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Journal articles on the topic 'FFPE bone marrow'

Author: Grafiati

Published: 10 September 2021

Last updated: 29 July 2025

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1

Chu, Lee Voon, Tse Hui Lim, Hein Than, et al. "Importance of Fluorescence in Situ Hybridization (FISH) Analysis on Bone Core Specimen for Detection of Relapse in Myeloid Malignancies with Fibrosis." Blood 144, Supplement 1 (2024): 6096. https://doi.org/10.1182/blood-2024-202353.

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Background and Aim:Patients with haematological disorders often require bone marrow aspirate (BMA) and trephine biopsy as part of diagnostics and assessment of disease relapse. Conventionally, marrow is assessed by morphology, immunophenotyping, cytogenetics, fluorescence in situ hybridization (FISH), and mutation analysis. However, in myeloid malignancies such as myelofibrosis or myelodysplastic syndrome (MDS) with fibrosis, BMA may be dry or haemodiluted without representative marrow fragments, leading to failure in analysis or inaccurate findings. In such instances, cut sections of bone cor

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2

Schiffman, Schiffman D., Jonathan Downie, Bradley Demarest, et al. "Novel Use of Molecular Inversion Probes to Interrogate Formalin-Fixed Paraffin-Embedded (FFPE) Samples of Childhood Leukemia." Blood 114, no. 22 (2009): 1589. http://dx.doi.org/10.1182/blood.v114.22.1589.1589.

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Abstract Abstract 1589 Poster Board I-615 Genome-wide, high-resolution analyses of copy number alterations (CNAs) now play an increasingly important role in identifying new genomic loci associated with leukemia biology and prognosis. The most powerful of these studies include large numbers of patients with associated clinical features and outcome data. Molecular Inversion Probes (MIPs) analyze genetic target sequences in parallel at the highest genomic resolution and can detect both gene copy number and allelic imbalance in clinical samples, and have been demonstrated to work on archived forma

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3

Reading, N. Scott, Archana M. Agarwal, Ronald Hoffman, Josef T. Prchal, and Mohamed E. Salama. "Transcriptional Characterization of Myelofibrotic Bone Marrow Microenvironment Reveals Distinct Tumor Microenvironment in JAK2+ and Calr+ PMF Marrows." Blood 128, no. 22 (2016): 1954. http://dx.doi.org/10.1182/blood.v128.22.1954.1954.

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Abstract Background: Primary myelofibrosis (PMF) is a clonal stem cell disorder associated with somatic mutations in three genes: Janus kinase 2 (JAK2), calreticulin (CALR) and thrombopoietin receptor (MPL). Although, our understanding of the microenvironment in PMF is limited, in PMF levels of Treg, cytotoxic T-cells, B-cells, macrophages and megakaryocyte cell populations have been reported to be elevated in either peripheral blood or bone marrow (BM) (Barosi Curr Hematol Malig Rep 2014). In addition, various cellular pathways including JAK/STAT, TGFβ1, and cytokine pathways (CXC family, hem

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4

Oetjen, Karolyn A., Diane E. Bender, Marianna B. Ruzinova, Stephen T. Oh, and Daniel C. Link. "Interrogating the Spatial Architecture of Human Bone Marrow Via Imaging Mass Cytometry." Blood 134, Supplement_1 (2019): 3728. http://dx.doi.org/10.1182/blood-2019-127460.

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Hematopoietic stem cell (HSC) proliferation, self-renewal, differentiation, and trafficking are dependent, in part, upon signals generated by stromal cells in the bone marrow. Stromal cells are organized into niches that support specific subsets of hematopoietic progenitors. Intimate interactions between HSCs and neighboring stromal cells coordinate hematopoietic responses during periods of physiologic stress, while also maintaining the lifelong integrity of the hematopoietic stem cell pool. Hematopoietic niches are comprised of a heterogeneous population of stromal and hematopoietic cells. Th

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5

Sadeghian, Mohammad Hadi, Maryam Mohammadnia Avval, Hossein Ayatollahi, et al. "Is There Any Relationship between Human Herpesvirus-8 and Multiple Myeloma?" Lymphoma 2013 (February 26, 2013): 1–5. http://dx.doi.org/10.1155/2013/123297.

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Background. Human herpesvirus-8 (HHV-8) is associated with some human diseases including Kaposi’s sarcoma and also some B-cell lymphoproliferative disorders. Few studies have highlighted the potential role of HHV-8 in the development of multiple myeloma (MM) which is known as a malignant proliferation of plasma cells derived from a single clone. Aims. The aim of this study was to find a relationship between HHV-8 and MM using polymerase chain reaction (PCR) method. Materials and Methods. This study was conducted on 30 formalin-fixed, paraffin-embedded (FFPE) bone marrow biopsies of multiple my

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6

Lawson, Michael, Yuji Ishitsuka, Andrew Pawlowski, et al. "Abstract 6169: High throughput in-situ spatial sequencing of proteins and RNA in FFPE tissue." Cancer Research 84, no. 6_Supplement (2024): 6169. http://dx.doi.org/10.1158/1538-7445.am2024-6169.

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Abstract We have developed an high throughput high resolution in situ multi-omic platform to enable studies in the rapidly evolving landscape of oncology and immunology research. Despite the potential of existing tools, the speed and throughput of current methodologies pose significant limitations. Here, we introduce a novel spatial sequencing platform employing a rapid 4-color SBS chemistry with sub-micron resolution imaging and an ultra-high throughput capacity. The platform simultaneously profiles RNA transcripts and proteins within formalin-fixed paraffin-embedded (FFPE) tissues. With up t

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7

Oetjen, Karolyn A., Diane E. Bender, Marianna B. Ruzinova, Daniel A. C. Fisher, Stephen T. Oh, and Daniel C. Link. "Imaging Mass Cytometry Reveals the Spatial Architecture of Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemias." Blood 136, Supplement 1 (2020): 44–45. http://dx.doi.org/10.1182/blood-2020-142238.

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Histologic review of bone marrow trephine biopsies is a central component of the diagnostic and treatment response evaluation of hematologic malignancies. Well-validated antibody reagents are routinely used for immunohistochemistry of these samples to provide additional insight into abnormal antigen expression. However, current immunohistochemistry staining protocols are typically limited to only one or two markers simultaneously. Dysplastic changes in cellular morphology and dyssynchronous expression of lineage markers are common features of myelodysplastic syndromes, myeloproliferative neopl

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8

Hobeck, Andrea Daniela, Sophia Wendt, Saskia Krohn, et al. "Comparative Analyses of Targeted Myeloid Cancer Next-Generation Sequencing Panel in Fresh Blood, Bone Marrow and FFPE Material." International Journal of Molecular Sciences 25, no. 6 (2024): 3534. http://dx.doi.org/10.3390/ijms25063534.

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Next-generation sequencing is a vital tool for personalized diagnostics and therapies in cancer. Despite numerous advantages, the method depends on multiple parameters regarding the sample material, e.g., sample fixation. A panel’s ability to ensure balanced pre-amplification of the regions of interest is challenging, especially in targeted sequencing approaches, but of significant importance to its applicability across hematological malignancies and solid tumors. This study comparatively evaluated the technical performance of the commercially available OncomineTM Myeloid Panel in fresh and Fo

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9

Shergill, Ardaman, Santosh L. Saraf, Sujata Gaitonde, Damiano Rondelli, and Irum Khan. "CCN2 - Exploring a New Biomarker in Myelofibrosis." Blood 126, no. 23 (2015): 4063. http://dx.doi.org/10.1182/blood.v126.23.4063.4063.

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Abstract BACKGROUND: Bone marrow fibrosis in myelofibrosis (MF) is the result of a complex and poorly understood interaction between megakaryocytes, fibroblasts, endothelial cells, cytokines and marrow stroma. Preclinical studies support a pathobiological role of TGF-β. It is overexpressed by megakaryocytes in MF and the TGF-β signature is upregulated and has been targeted in MF animal models. However TGF-β is a pleiotropic cytokine implicated in many cellular processes. CCN proteins are a group of 6 matricellular proteins important in fibrotic diseases and injury repair. CCN1 (CYR61) and CCN2

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10

Hirschbühl, Klaus, Bruno Märkl, Gernot Müller, et al. "Molecular Genetic Analysis of Bone Marrow Core Biopsy as an Alternative or Adjunct to Bone Marrow Aspirate and/or Peripheral Blood in Hematologic Myeloid Neoplasms." Diagnostics 15, no. 8 (2025): 991. https://doi.org/10.3390/diagnostics15080991.

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Background: The diagnosis of hematologic neoplasms is usually based on a synopsis of the peripheral blood (PB) and bone marrow findings. Morphology continues to be the cornerstone, but genetic analysis plays an increasingly important role. In routine workup, molecular genetic analysis is performed from a bone marrow aspirate (BMA). In the event of inadequate aspiration, PB is used. Not infrequently, however, PB only partially represents the disease. In this situation, molecular genetic analysis of formalin-fixed and paraffin-embedded (FFPE) bone marrow core biopsy (BMCB) could be a better alte

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11

Loya, Matthew, Tine Casneuf, Helene Bon, et al. "Abstract 2990: Single-slide FFPE proteomic profiling enables therapeutic target quantification and molecular subtyping in non-Hodgkin’s lymphoma and bone marrow tumor biopsies." Cancer Research 85, no. 8_Supplement_1 (2025): 2990. https://doi.org/10.1158/1538-7445.am2025-2990.

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Abstract Molecular profiling of formalin-fixed paraffin-embedded (FFPE) tumors in clinical research is performed with low-plex immunohistochemistry or genome-wide transcriptomics. The application of unbiased, highly multiplexed proteomics to FFPE is limited by sample input requirements, assay throughput and complex bioinformatics. Here we report a proteomic method amenable to low-input FFPE profiling which complements transcriptomics. We applied Biognosys’ mass-spectrometry platform (TrueDiscovery, DIA-MS) to samples encountered in routine histopathology laboratories (e.g. B-cell malignancies

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12

Neat, Michael J., Mufaddal T. Moonim, Robert G. Dunn, Helen Geoghegan, and Nicola J. Foot. "Fluorescence in situ hybridisation analysis of bone marrow trephine biopsy specimens; an additional tool in the diagnostic armoury." Journal of Clinical Pathology 66, no. 1 (2012): 54–57. http://dx.doi.org/10.1136/jclinpath-2012-201131.

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Fluorescence in situ hybridisation (FISH) analysis is now widely employed in the diagnosis and risk stratification of a wide range of malignant diseases. While this technique is used successfully with formalin-fixed paraffin-embedded (FFPE) sections from numerous tissue types, FISH analysis of FFPE tissue sections from trephine biopsy specimens has been less widely reported, possibly due to technical limitations relating to the decalcification protocols employed. During the last 4 years FISH analysis has been carried out successfully in 42 out of 55 (76%) consecutive trephine biopsy specimens

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13

Annibali, Ombretta, Monica Di Cecca, Martina Verri, et al. "T Cell Ig and ITIM Domains (TIGIT) Expression in Multiple Myeloma." Blood 142, Supplement 1 (2023): 6607. http://dx.doi.org/10.1182/blood-2023-189171.

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Background Neoplastic myeloma cells show a wide variety of mechanisms that induce the microenvironment, allowing immune evasion and promoting their proliferation, survival, migration and drug resistance. In this context, immunocheckpoints are particularly important, representing the modulators of signal pathways responsible for immune tolerance, a mechanism that prevents the destruction of cancer cells by the immune system. T cell Ig and ITIM domains (TIGIT), a member of the poliovirus (PVR) /nectin receptor family, is a new immune checkpoint that negatively regulates T cell functions. In Mult

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14

Martinez, Nerea, Carmen Almaraz, Manuela Mollejo, et al. "Mutational Status of Splenic Diffuse Red Pulp Small B-Cell Lymphoma Revealed By Whole Exome Sequencing." Blood 126, no. 23 (2015): 1448. http://dx.doi.org/10.1182/blood.v126.23.1448.1448.

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Abstract Background: Splenic diffuse red pulp lymphoma (SDRPL) is a rare small B cell neoplasm provisionally included in a category of unclassifiable splenic B-cell lymphoma/leukemias in the 2008 WHO classification. SDRPL is characterized by a diffuse pattern of involvement of the splenic red pulp by small monomorphous B lymphocytes. Patients are normally diagnosed at stage IV when spleen, bone marrow and peripheral blood are involved. This indolent but incurable disease is more common in aged males and it shows with splenomegaly and moderate lymphocytosis. The differential diagnosis with othe

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15

Crassini, Kyle R., Yandong Shen, William S. Stevenson, Stephen P. Mulligan, Oliver Giles Best, and Richard Christopherson. "mRNA Profiling of CLL Cells Derived from the Blood, Bone Marrow and Lymph Node." Blood 132, Supplement 1 (2018): 1850. http://dx.doi.org/10.1182/blood-2018-99-118264.

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Abstract Background Chemo-immunotherapy remains the backbone of therapy for patients with chronic lymphocytic leukaemia (CLL), with evidence pointing towards long term remission and even cure in patients with mutated IGHV status receiving this therapy frontline (1). However, relapse is common especially in those harbouring abnormalities in TP53 or ATM, unmutated IGHV status or a complex karyotype (2). It has become increasingly apparent that the bone marrow (BM) and lymph node (LN) play important roles in promoting the survival and proliferation of CLL cells. Signalling pathways triggered by i

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16

Horna, Pedro, Kathryn E. Pearce, Rhett P. Ketterling, and Jess Peterson. "Recurrent Chromosomal Abnormalities in Tumoral Lesions of Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia: A Large-Scale Fluorescent in-Situ Hybridization Study on Tissue Biopsy Sections." Blood 134, Supplement_1 (2019): 4282. http://dx.doi.org/10.1182/blood-2019-129116.

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Background: Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) is a lymphoproliferative disorder of small mature B-cells, most commonly presenting with peripheral blood and bone marrow involvement. Tumoral lesions are variably encountered, resulting from either lymph node involvement or, less commonly, infiltration into virtually any extramedullary site. The prognostic assessment of patients with SLL/CLL relies strongly on the identification of recurrent chromosomal abnormalities, which are routinely tested by fluorescence in situ hybridization (FISH) on peripheral blood or bone

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17

Nath, Shriram Vaidia, Michelle Tamblyn, Susan Telfer, et al. "Ethylene Diamine Tetra Acetic Acid (EDTA) Decalcification of Paediatric Bone Marrow Trephines In a Diagnostic Laboratory." Blood 116, no. 21 (2010): 2566. http://dx.doi.org/10.1182/blood.v116.21.2566.2566.

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Abstract Abstract 2566 Background: In paediatric patients with haematological disorders such as acute lymphoblastic leukaemia (ALL), bone marrow aspiration is sometimes difficult to obtain and bone marrow trephine biopsy (BMTB) is a valuable source of material. In a diagnostic laboratory, the turnaround time is critical for a bone marrow trephine to be decalcified, processed and embedded. In our laboratory, 48 hours was routinely required from the time the bone marrow was performed until the sections were ready for reporting. A hydrochloric acid-EDTA (Ethylene-Diamine-Tetra-Acetic acid) decalc

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18

Zhang, Anqi, Ting Sun, Renchi Yang, and Lei Zhang. "Comparative Analysis of Bone Marrow Microbiome and Proteome Differences between Essential Thrombocythaemia and Prefibrotic Primary Myelofibrosis." Blood 142, Supplement 1 (2023): 4577. http://dx.doi.org/10.1182/blood-2023-189072.

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Background Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are hematologic malignancies with a hallmark feature of chronic inflammation. MPNs mainly include polycythaemia vera (PV), essential thrombocythaemia (ET), primary myelofibrosis (PMF) and prefibrotic primary myelofibrosis (pre-PMF). In contrast to ET, an accurate morphological diagnosis of pre-PMF is a key issue due to its worse prognosis. However, it is difficult to accurately diagnose pre-PMF, mainly relying on pathological diagnosis. The heavy reliance on morphology for accurate diagnosis poses a challenge to th

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19

dos Santos, David Cordas, Junko Tsuji, Yoshinobu Konishi, et al. "P-203 Ability To Perform Spatial Transcriptomics in FFPE Decalcified Bone Marrow Samples of Patients With Precursor Myeloma." Clinical Lymphoma Myeloma and Leukemia 24 (September 2024): S154—S155. http://dx.doi.org/10.1016/s2152-2650(24)02106-2.

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20

Locke, Darren, Steven Bernstein, Frank Lynch, et al. "An IHC Screen For EphA3 Positive FFPE Tumors." Blood 122, no. 21 (2013): 4965. http://dx.doi.org/10.1182/blood.v122.21.4965.4965.

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Abstract Eph receptors are the largest subgroup of the receptor tyrosine kinases (RTK). Unlike other RTK, these function principally during development. Quiescent in postembryonic tissues, Eph expression by adult tissues is abnormal and implicated in tumor initiation, invasion and metastasis. Aberrant EphA3 expression is seen in solid and hematologic tumors, particularly advanced stage lymphoproliferative and myeloproliferative diseases. In this regard, targeting EphA3 may constitute a novel treatment for hematological malignancy. With clinical utility in mind, i.e., patient selection for anti

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21

Giger, N., M. Schröder, D. Arens, et al. "SPATIAL TRANSCRIPTOMICS WORKFLOW ENABLES DISTINCT TISSUE-SPECIFIC MOLECULAR CHARACTERIZATION OF NONUNION AND UNION BONE FRACTURES IN MICE." Orthopaedic Proceedings 106-B, SUPP_18 (2024): 113. http://dx.doi.org/10.1302/1358-992x.2024.18.113.

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BackgroundThe molecular mechanisms underlying non-union bone fractures largely remain elusive. Recently, spatial transcriptomics approaches for musculoskeletal tissue samples have been developed requiring direct placement of histology sections on barcoded slides. However, Formalin-Fixed-Paraffin-Embedded (FFPE) bone sections have been associated with limited RNA quality and read depth compared to soft tissue. Here, we test spatial transcriptomics workflows based on transcriptomic probe transfer to characterize molecular features discriminating non-union and union bone fractures in mice.MethodH

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Kobayashi, Nobuhiko, Tsukasa Oda, Makiko Takizawa та ін. "Integrin α7 and Extracellular Matrix Laminin 211 Interaction Promotes Proliferation of Acute Myeloid Leukemia Cells and Is Associated with Granulocytic Sarcoma". Cancers 12, № 2 (2020): 363. http://dx.doi.org/10.3390/cancers12020363.

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Acute myeloid leukemia (AML) with granulocytic sarcoma (GS) is characterized by poor prognosis; however, its underlying mechanism is unclear. Bone marrow samples from 64 AML patients (9 with GS and 55 without GS) together with AML cell lines PL21, THP1, HL60, Kasumi-1, and KG-1 were used to elucidate the pathology of AML with GS. RNA-Seq analyses were performed on samples from seven AML patients with or without GS. Gene set enrichment analyses revealed significantly upregulated candidates on the cell surface of the GS group. Expression of the adhesion integrin α7 (ITGA7) was significantly high

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23

Mangaonkar, Abhishek A., Terra L. Lasho, Justin Boysen, et al. "Cellular Interactions within Clonal Dendritic Cell Aggregates Drive Immune Tolerance in Chronic Myelomonocytic Leukemia Bone Marrow Microenvironment." Blood 142, Supplement 1 (2023): 4077. http://dx.doi.org/10.1182/blood-2023-186856.

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Introduction: Clonal dendritic cell (DC) aggregates in chronic myelomonocytic leukemia (CMML) are seen in approximately 20-30% patients at diagnosis. Previously, these were thought to be comprised of CD123+ plasmacytoid DCs but our data has suggested that these are heterogenous and comprise of myeloid DCs, monocytes, and myeloid-derived suppressor cells. Furthermore, these aggregates uniformly express immune checkpoints such as indoleamine 2,3-dioxygenase-1 (IDO), associate with an IDO-specific systemic impact (increased trytophan catabolism), and expanded regulatory T cell population in CMML,

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24

Flodr, Patrik, Pavla Latalova, Petra Pusciznova, et al. "Multiple Myeloma and Bone Marrow Microenvironment Immunohistochemical Study of the Expression of 15 Proteins Related to Myeloma Bone Disease." Blood 126, no. 23 (2015): 5318. http://dx.doi.org/10.1182/blood.v126.23.5318.5318.

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Abstract Objective: Neoplastic milieu is an integral part of all malignant diseases including multiple myeloma and plays variable role in their development, retention/adhesivity, resistency or sensitivity to therapeutic approach, homing and also paraneoplastic manifestations. Relatively genetically stable milieu may play an important role in new specific molecular therapeutic approaches and therefore should be contextually studied with neoplastic cells as complex neoplastic tissues. The expressions of 15 proteins with close relation to the development of myeloma bone disease (MBD) were analyse

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25

Duncan, Ian, Natalie Danziger, Daniel Duncan, et al. "Acid-Based Decalcification Methods Compromise Genomic Profiling from DNA and RNA." Blood 134, Supplement_1 (2019): 4659. http://dx.doi.org/10.1182/blood-2019-131362.

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BACKGROUND: Comprehensive genomic profiling (CGP) performed by next-generation sequencing of DNA detects genomic alterations including point mutations, insertions/deletions, copy number variations, and select gene rearrangements. When RNA sequencing is included in CGP, it allows for expanded detection of gene fusions, which are common in hematologic malignancies and sarcomas. When such tumors involve bone, a decalcification step is frequently employed to soften tissues prior to processing and sectioning. While commonly used acid-based decalcification methods work quickly, the resulting nucleic

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Maurer, Katie, Florian Raths, Kenneth Gouin, et al. "Deconvolving Immunologic Networks of the AML Marrow Microenvironment with Spatial Multi-Omic Profiling." Blood 144, Supplement 1 (2024): 928. https://doi.org/10.1182/blood-2024-204226.

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The spatial organization of “immune hubs” in tumor microenvironments has gained recognition across histologies and tissues. Bone marrow offers a valuable platform for investigating immune hubs in the context of acute myeloid leukemia (AML) following hematopoietic stem cell transplant (HSCT). This setting may provide fresh insights into mechanisms of relapse and maintenance of remission after donor lymphocyte infusion (DLI). While it is generally understood that DLI exerts its effects through a graft-versus-leukemia (GVL) response, the specific cellular players and spatial organization driving

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27

Dhakal, Binod, Shruti Sharma, Svetlana Shchegrova, et al. "Personalized, ctDNA analysis to detect minimal residual disease and identify patients at high risk of relapse with multiple myeloma." Journal of Clinical Oncology 39, no. 15_suppl (2021): 8029. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.8029.

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8029 Background: Despite treatment with high-dose chemotherapy followed by autologous stem cell transplantation (AHCT), MM patients invariably relapse. MRD-negativity post-AHCT has emerged as the most important prognostic marker. Currently, MRD in MM is monitored via bone marrow aspirate sampling. Marrow MRD assays are limited by the spatial heterogeneity of marrow MM localization; extramedullary disease and sampling variability of marrow aspiration. Sensitive, non-invasive blood-based MRD assay is an unmet need. ctDNA as a noninvasive biomarker can be utilized to predict relapse in MM. Here w

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28

Lee, Sze Hwei, Tai-Chung Huang, Yuan Chang-Tsu, et al. "Discrepant Mutational Composition between Myeloid Sarcoma and Bone Marrow Leukemia Revealed through Targeted Next Generation Sequencing." Blood 132, Supplement 1 (2018): 1395. http://dx.doi.org/10.1182/blood-2018-99-116637.

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Abstract Introduction: Myeloid sarcoma (MS) is the involvement of acute myeloid leukemia (AML) cells in extramedullary tissues, whose mechanism remains to be further elucidated. How MS affects AML prognosis at a molecular level is also an open question. This unexplained tropism of leukemic blasts to extramedullary tissues is likely caused by the combination of genetic and epigenetic aberrations. Our study investigated the paired samples of myeloid sarcoma tissue and bone marrow (BM) at diagnosis in perspective of elucidating specific genetic abnormalities that underpin the ectopic homing of MS

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Zhang, Wei, Min Xiao, Jianfeng Zhou, and Ken H. Young. "Targeted Next-Generation Sequencing of Cell-Free DNA in Diffuse Large B-Cell Lymphoma." Blood 132, Supplement 1 (2018): 4212. http://dx.doi.org/10.1182/blood-2018-99-116847.

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Abstract Background: Minimal residual disease (MRD) has an emerging diagnostic and prognostic role in Diffuse Large B-cell Lymphoma (DLBCL). However, repetitious bone marrow aspirations or lymph node biopsies would bring great pains to patients. At present, deep next-generation sequencing (NGS) based on circulating tumor DNA (ctDNA), allows quantitative mutational analysis with high sensitivity simultaneously, thereby providing us a promising non-invasive and radiation-free approach to monitor MRD and track sophisticated dynamic evolution of tumor clones. Methods: A total of 21 patients with d

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Chen, Jian, Ryan Ripsman, Rose Vernier, Astra Schwertschkow, Adam Shlien, and Johann K. Hitzler. "Expansion of GATA1-Mutant Clones in Blood Samples of Patients with Transient Abnormal Myelopoiesis (TAM) during Clinical Follow up Heralds Transformation to Myeloid Leukemia Associated with Down Syndrome (ML-DS)." Blood 144, Supplement 1 (2024): 6137. https://doi.org/10.1182/blood-2024-204116.

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Background. Children with Down syndrome have a 150-fold increased incidence of myeloid leukemia. Myeloid leukemia associated with Down syndrome (ML-DS) evolves from a subclone of the neonatal preleukemic disorder transient abnormal myelopoiesis (TAM). TAM is initiated when somatic GATA1 mutations occur in fetal hematopoietic progenitors with trisomy 21. Co-operating mutations in genes coding for cohesin complex genes, epigenetic modifiers and signal transducers propel transformation of TAM to ML-DS in approximately 20 % of patients, typically during the first four years of life. GATA1 mutation

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Le Bris, Yannick, Anne Moreau, Audrey Ménard, et al. "Comprehensive Analysis of the Tumoral and Microenvironmental Transcriptome of Lymph Nodes and Bone Marrow in Mantle Cell Lymphoma." Blood 138, Supplement 1 (2021): 2405. http://dx.doi.org/10.1182/blood-2021-151041.

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Abstract The Reverse Transcription Multiplex Ligation-dependent Probe Amplification (RT-MLPA) technique is a method allowing for the semi-quantitative concomitant analysis of a number of transcripts of interest in cells or tissues. It relies on the amplification of complementary DNA (cDNA) derived from messenger ribonucleic acid (mRNA) after binding and ligation of specific probes on adjacent regions. It is thus applicable to the relatively fragmented low-quality RNA that can be derived from formalin-fixed paraffin embedded samples (FFPE), ill adapted to other methods such as RNASeq. Adequate

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32

Greene, John Patrick, Orla Casey, Karen O'Leary, et al. "The Irish Programme for Stratified Prostate Cancer Therapy (iPROSPECT)." Journal of Clinical Oncology 34, no. 2_suppl (2016): 335. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.335.

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335 Background: iPROSPECT is a prospective longitudinal translational study, funded through the Irish Cancer Society in partnership with Movember that is examining blood and tissue markers that might correlate with treatment response and survival and aid future stratification of metastatic prostate cancer (mPCa) patients with regard to optimal personalised treatment regimens. Methods: Patients with metastatic prostate cancer who are beginning or changing treatment are eligible for inclusion. Nine hospital sites supported by four research laboratories are open to recruitment. Cohort 1 (n = 15)

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Locke, Darren, Frank Lynch, Steven Bernstein, Koushan Siami-Namini, and Geoff T. Yarranton. "An IHC Screen for EphA3 Positive Myelofibrosis (MF) and Other Myeloproliferative Neoplasms (MPNs)." Blood 124, no. 21 (2014): 5588. http://dx.doi.org/10.1182/blood.v124.21.5588.5588.

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Abstract MF is a neoplastic stem cell disorder in which a multipotent hematopoietic stem cell acquires a clonal proliferative advantage, and its progeny inappropriately releases fibrogenic factors into the bone marrow microenvironment, leading to secondary bone marrow fibrosis. The cytokines implicated in the pathogenesis of MF include transforming growth factor β (TGF-β), basic fibroblastic growth factor (b-FGF), and platelet-derived growth factor (PDGF). Some of these cytokines, such as b-FGF and PDGF can act as angiogenic factors. Patients with MF have higher concentrations of circulating v

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Snyder, Matthew J., William D. Bradford, Priya S. Kishnani, and Laura P. Hale. "Idiopathic Hyperammonemia following an Unrelated Cord Blood Transplant for Mucopolysaccharidosis I." Pediatric and Developmental Pathology 6, no. 1 (2003): 78–83. http://dx.doi.org/10.1007/s10024-001-0271-3.

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Bone marrow transplantation (BMT) has been shown to reverse or stabilize some manifestations of mucopolysaccharidosis I (Hurler syndrome). Idiopathic hyperammonemia (IHA) is a rare complication of solid organ and BMT that is characterized by elevated serum ammonia, normal liver enzymes, and abrupt onset of neurologic deterioration. We present the case of a 14-month-old male patient with Hurler syndrome who developed fatal IHA (ammonia = 2297 μmol/L) 31 days after a cord blood transplant. A complete autopsy was performed, with examination of both frozen and formalin-fixed paraffin-embedded (FFP

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Clarke, Scott T., Mae Voeun, Leticia Montoya, Chris Vonnegut, and Bhaskar Mandavilli. "Abstract 3769: Spatial biology in situ hybridization and multiplexed immunohistochemistry detection compatibility using a modified protocol." Cancer Research 84, no. 6_Supplement (2024): 3769. http://dx.doi.org/10.1158/1538-7445.am2024-3769.

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Abstract In the field of spatial-omics imaging, combining mRNA in situ hybridization (ISH) detection with multiplexed protein immunohistochemistry detection (IHC) is desirable. We present a simplified workflow in FFPE tissue sections where ISH is detected using branched ssDNA signal amplification visible by brightfield imaging combined with multiplexed IHC using directly labeled antibodies detected by fluorescence. In multiple studies mRNA expression of PCNA (Proliferating Cell Nuclear Antigen) shows moderate to high nuclear positivity observed in most cancer cells, with gliomas and lymphomas

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Gooding, Sarah, Chen-Yi Wang, Warren Baker, et al. "Development of a Spatial Multiomics Platform to Integrate Genomic, Transcriptomic and Proteomic Features for Translational Research in Multiple Myeloma." Blood 144, Supplement 1 (2024): 6848. https://doi.org/10.1182/blood-2024-205264.

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Multiple Myeloma (MM) is a genomically heterogeneous cancer of malignant plasma cells (PC) residing in the bone marrow. Despite recent therapeutic advances, it is incompletely understood why some patient populations remain largely therapy-refractory or relapse, even with targeted immunotherapies. Whilst MM classification based on genomic features and gene expression profiling (GEP) is well-described, the role of spatial interactions between tumour cells and the bone marrow tumour microenvironment (TME) in dictating treatment responses is insufficiently defined. Spatial heterogeneity in MM was

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Reading, N. Scott, Josef T. Prchal, Ronald Hoffman, and Mohamed E. Salama. "Digital Immune Expression Profiling Coupled with Immunohistochemistry for Interrogation of Microenvironment in Formalin Fixed Paraffin Embedded Specimens of Marrow and Spleen from PMF Patients." Blood 126, no. 23 (2015): 2832. http://dx.doi.org/10.1182/blood.v126.23.2832.2832.

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Abstract Background: Gene expression profiling studies have demonstrated aberrant expression of inflammatory response genes in myeloproliferative neoplasm (MPN) granulocytes and/or CD34+ cells. Our understanding of the immune response to primary myelofibrosis (PMF) hematopoietic stem cells and tissue-specific microenvironments is not complete due to a limited availability of bone marrow (BM) aspirates and fresh spleen samples from PMF patients. In order to overcome this obstacle, we utilized a novel approach with mRNA enrichment analysis which utilizes formalin fixed, paraffin embedded (FFPE)

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Maciocia, Paul, Margarida Neves, Shimobi Onuoha, et al. "Analysis of T-Cell Receptor Beta-Constant Region Expression for Rapid Assessment of T-Cell Clonality." Blood 132, Supplement 1 (2018): 2867. http://dx.doi.org/10.1182/blood-2018-99-112569.

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Abstract Introduction T-cell malignancies are heterogenous disorders, representing approximately 10-15% of cases of non-Hodgkin's lymphoma and 15% of acute lymphoblastic leukaemia. Diagnosis may be complicated both by the fact that non-malignant oligoclonal T-cell proliferations often mimic T-cell cancers, and due to the lack of consistent markers of malignancy which discriminate healthy and malignant T-cells. B-cell lymphoproliferations, by contrast, can be reliably identified as clonal by confirmation of restricted kappa or lambda light chain expression. We have recently described an analogo

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Raman, Indu, Cavan Bennett, Surender Juneja, Costas K. Yannakou, Tishya Indran, and Sant-Rayn Pasricha. "Dysregulated Complement Activation in Polycythemia Vera: A Novel Mechanism for Thrombosis in Myeloproliferative Neoplasms Uncovered By Proteomic Analysis." Blood 144, Supplement 1 (2024): 4517. https://doi.org/10.1182/blood-2024-206614.

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Introduction: Myeloproliferative neoplasms (MPNs) are a group of disorders associated with an increased risk of thrombosis, with polycythemia vera (PV) considered to carry the highest risk. This study aims to investigate potential mechanisms underlying the increased thrombotic risk in MPNs through mass spectrometry-based proteomic analysis of bone marrow trephines. Methods: We conducted data-independent acquisition (DIA) proteomic analysis on archived, formalin-fixed paraffin-embedded (FFPE) bone marrow trephine samples from 60 MPN patients (20 with PV, 20 with essential thrombocythemia [ET],

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Georg, Greiner, Michael Gurbisz, Franz Ratzinger, et al. "Molecular Quantification of Tissue Mast Cell Burden in Systemic Mastocytosis: A New Approach for Diagnostics and Prognostication." Blood 132, Supplement 1 (2018): 3043. http://dx.doi.org/10.1182/blood-2018-99-116492.

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Abstract Background: The somatic KIT D816V mutation leads to an activation of the receptor tyrosine kinase KIT and represents a diagnostic criterion for systemic mastocytosis (SM). In the majority of patients, only a very few KIT D816V+ mast cells (MC) or MC precursors, if any, are found in peripheral blood (PB) and bone marrow (BM) aspirates. In contrast, the MC count in BM biopsies is typically much higher. Melting curve analysis after peptide nucleic acid-mediated PCR clamping (clamp-PCR) is widely used for detecting KIT mutations in biopsies.1 We have previously proposed dPCR as a new stan

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Danziger, Natalie, Chelsea Marcus, Jessica Lee, et al. "Comprehensive Genomic Profiling of Mature B-Cell Lymphomas/Leukemias: Foundation One Heme Reveals Actionable Alterations and Biomarkers." Blood 144, Supplement 1 (2024): 6191. https://doi.org/10.1182/blood-2024-209066.

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Introduction: Molecular profiling of mature B-cell lymphomas and leukemias informs diagnosis, prognosis, and therapy. For example, WHO and NCCN guidelines designate specific genomic alterations, such as TP53 mutations in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), as essential for risk stratification. Gene rearrangements, including those involving IRF4, CCND1, BCL2, BCL6, and MYC, also have diagnostic and prognostic significance for B-cell neoplasms. We analyzed the genomic landscape of a large cohort of mature B-cell lymphomas/leukemias tested on the FoundationOne Heme

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Kuo, Szu-Yin, Hongxiang Liu, Yung-Liang Liao, et al. "A parallel comparison of T-cell clonality assessment between an in-house PCR assay and the BIOMED-2 assay leading to an efficient and cost-effective strategy." Journal of Clinical Pathology 64, no. 6 (2011): 536–42. http://dx.doi.org/10.1136/jcp.2010.086637.

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AimsDiagnosis of T-cell lymphoproliferation is sometimes challenging, and in certain instances pathologists rely heavily on the clonality assessment results of T-cell receptor (TCR) gene rearrangement (TCR-GR). Many investigators have designed various in-house primer sets for PCR-based study targeting different loci of TCR genes. In recent years, the commercial BIOMED-2 protocols have become available. The in-house primers are very cheap while the BIOMED-2 primers are expensive. This parallel study aimed to compare the sensitivity of the in-house TCRG primers (two reactions) and the BIOMED-2 T

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Wen, Yu-Ye, Erica Fang, Yanchun Li, Condie Edwin Carmack, and Marilyn M. Li. "The efficacy of targeted next-generation sequencing for detection of clinically actionable mutations in cancer." Journal of Clinical Oncology 30, no. 15_suppl (2012): 10598. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.10598.

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10598 Background: The emergence of next-generation sequencing (NGS) technologies has significantly accelerated the identification of cancer-causing mutations and the development of personalized cancer care. However, the clinical application of these technologies to detect cancer gene mutations has been extremely limited due to the long turn around time, the high cost, and large amount of input DNA required by existing NGS-based tests. Methods: We have assessed the performance of a novel NGS technology that merges multiplex PCR with ion semiconductor sequencing (AmpliSeq, Life Technologies, Inc

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Daniel, Sugganth, Erica Gornstein, Garrett Michael Frampton, et al. "BRCA1/2 reversion mutations in prostate cancer identified from clinical tissue and liquid biopsy samples." Journal of Clinical Oncology 35, no. 15_suppl (2017): 5024. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.5024.

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5024 Background: Prostate tumors with genomic alterations (GA) in BRCA1 or BRCA2 ( BRCA) may be sensitive to treatment with PARP inhibitors (PARPi). However, secondary reversion mutations (revGA) can arise that may restore BRCA function and underlie reduced sensitivity to PARPi or platinum (Pt)-based therapy. Comprehensive genomic profiling (CGP), using either tissue or liquid biopsies, can detect the variety of clinically relevant revGA that can arise. Methods: DNA extracted from FFPE tumor tissue or blood samples obtained during routine clinical care for 1911 patients with predominantly rela

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Mason, Emilia O., David Coffey, Arjun Raj Rajanna, et al. "Artificial Intelligence of the 2-D and 3-D Bone Marrow Microenvironment to Identify Cytogenetic Subtypes of Multiple Myeloma." Blood 142, Supplement 1 (2023): 7163. http://dx.doi.org/10.1182/blood-2023-188324.

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Multiple myeloma is the second most common hematologic malignancy with an annual incidence of 35,000 new cases every year in the U.S. Due to improved access to effective therapies, overall survival has improved from 1-3 years to over 10-20 years. However, there is not yet any available curative therapy for multiple myeloma and most patients will suffer from recurrent relapses, with an unmet clinical need for novel therapies. The interplay between the bone marrow microenvironment and malignant plasma cells is critically important to better understand pathogenesis of the disease, to predict resp

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Castorena, Jimena, Christophe Desterke, Barbara Burroni, et al. "Spatial Transcriptomic Profiling of Bone Marrow Vascular Niches Unveils an Endothelial Stress Signature in Myeloproliferative Neoplasms." Blood 144, Supplement 1 (2024): 4516. https://doi.org/10.1182/blood-2024-210924.

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Introduction: Bone marrow endothelial cells (BMECs) are not only key contributors to normal hematopoiesis but also play an important role in the pathogenesis of myeloid diseases, as in the case of Philadelphia-negative myeloproliferative neoplasms (MPNs), where vascular complications, such as thrombosis and angiogenesis, are a mayor clinical challenge. Single cell technologies have contributed to understand the transcriptional heterogeneity of the hematopoietic MPN malignant clones (O'Sullivan, J. et al., Blood, 2023) and is starting to shed light on niche stromal cells. However, the spatial c

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Pardo, Makayla, Dennis Bonal, Seo-Ho Lee, et al. "Abstract P08: 10x spatial transcriptomics of human AML core bone marrow biopsies reveals the complex remodeling of the non-hematopoietic stromal microenvironment post-treatment." Blood Cancer Discovery 5, no. 2_Supplement (2024): P08. http://dx.doi.org/10.1158/2643-3249.bcdsymp24-p08.

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Abstract Acute myeloid leukemia (AML) is a heterogeneous myeloid malignancy with a 5-year survival rate less than 26% due to poor response to treatment and relapse. Leukemic stem cells, largely responsible for relapse, exist in a highly specialized bone marrow (BM) microenvironment. Recent studies have described specific alterations to the non-hematopoietic BM niche following AML progression, such as an increase in mesenchymal stem cells and reduction in osteogenesis. While it is known that stromal cells support development of myeloid malignancies, it remains unclear how they contribute to dis

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Shirane, Shuichi, Marito Araki, Soji Morishita, et al. "Dynamic Increase in JAK2V617F Allele Burden Is a Predictive Parameter for the Transformation into Myelofibrosis from Polycythemia Vera and Essential Thrombocytosis." Blood 124, no. 21 (2014): 1832. http://dx.doi.org/10.1182/blood.v124.21.1832.1832.

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Abstract Patients diagnosed with polycythemia vera (PV) or essential thrombocythemia (ET), a subtype of myeloproliferative neoplasms (MPN), sometimes suffer disease transformation into myelofibrosis (MF) associated with poorer prognosis. Thus, predicting which patients have a risk of MF transformation is an important task. Following the identification of a driver mutation JAK2V617F in a majority of MPN patients, several studies was performed to investigate the potential of JAK2V617F allele burden as a diagnostic marker for MF-transformation. However, the results differ between cohorts presumab

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Wang, Katelyn, Iran Rashedi, James T. England, et al. "Dynamic Stromal Changes in Myelofibrosis Patients Pre/Post JAK Inhibition Is Revealed in Clinically Archived Bone Marrow Biopsies By Smooth Muscle Actin (SMA)-CD34 Dual Immunohistochemistry." Blood 138, Supplement 1 (2021): 3286. http://dx.doi.org/10.1182/blood-2021-151458.

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Abstract The natural history of BCR-ABL1 negative myeloproliferative neoplasms (MPNs) is progression towards an overt myelofibrotic (MF) phase with variable risk to develop secondary acute myeloid leukemia. Current treatments include Janus kinase inhibitors (JAKi) which can temporarily alleviate MF-related symptoms but are non-curative and most patients eventually progress to a more advanced stage. Given the negative prognostic impact of bone marrow fibrosis in MPNs and generally poor outcome post JAKi failure, it would be important to identify in situ biomarkers that address the initiation, p

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Murakami, Kosuke, Hirofumi Ando, Michele Doucet, Dacheng Ding, William Huang, and Sudipto Ganguly. "Abstract 165: PVRL2 upregulation by tumor-associated macrophages confers a regulatory phenotype and is associated with poor prognosis in high-grade serous ovarian cancer." Cancer Research 84, no. 6_Supplement (2024): 165. http://dx.doi.org/10.1158/1538-7445.am2024-165.

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Abstract Advanced or recurrent high-grade serous ovarian cancer (HGSOC) are associated with poor prognosis. While HGSOC is moderately immunogenic, anti-PD-1/L1 therapy has fared poorly in trials. PVRL2 (Nectin2) is both a cell-adhesion molecule as well as a ligand for PVRIG, a novel co-inhibitory receptor. While PVRL2 is constitutively expressed by epithelial/tumor cells, it can also be upregulated by macrophages. Whether macrophage-expressed PVRL2 functions exclusively as an immunoregulatory ligand in HGSOC is not known. CD45+ tumor infiltrate from 6 treatment-naïve and 3 neoadjuvant chemothe

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