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1

de Rooij, Laura P. M. H., Derek C. H. Chan, Ava Keyvani Chahi, and Kristin J. Hope. "Post-transcriptional regulation in hematopoiesis: RNA binding proteins take control." Biochemistry and Cell Biology 97, no. 1 (2019): 10–20. http://dx.doi.org/10.1139/bcb-2017-0310.

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Normal hematopoiesis is sustained through a carefully orchestrated balance between hematopoietic stem cell (HSC) self-renewal and differentiation. The functional importance of this axis is underscored by the severity of disease phenotypes initiated by abnormal HSC function, including myelodysplastic syndromes and hematopoietic malignancies. Major advances in the understanding of transcriptional regulation of primitive hematopoietic cells have been achieved; however, the post-transcriptional regulatory layer that may impinge on their behavior remains underexplored by comparison. Key players at
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Stellrecht, C. M., G. Fraizer, C. Selvanayagam, L. Y. Chao, A. Lee, and G. F. Saunders. "Transcriptional regulation of a hematopoietic proteoglycan core protein gene during hematopoiesis." Journal of Biological Chemistry 268, no. 6 (1993): 4078–84. http://dx.doi.org/10.1016/s0021-9258(18)53582-1.

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3

Choi, Kyunghee. "Hemangioblast development and regulation." Biochemistry and Cell Biology 76, no. 6 (1998): 947–56. http://dx.doi.org/10.1139/o99-007.

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Hematopoietic and endothelial cell lineages are the first to mature from mesoderm in the developing embryo. However, little is known about the molecular and (or) cellular events leading to hematopoietic commitment. The recent applications of technology utilizing gene targeted mice and the employment of many available in vitro systems have facilitated our understanding of hematopoietic establishment in the developing embryo. It is becoming clear that embryonic hematopoiesis occurs both in the extra-embryonic yolk sac and within the embryo proper in the mouse. The existence of the long pursued h
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Gandillet, Arnaud, Alicia G. Serrano, Stella Pearson, Michael Lie-A-Ling, Georges Lacaud, and Valerie Kouskoff. "Sox7-sustained expression alters the balance between proliferation and differentiation of hematopoietic progenitors at the onset of blood specification." Blood 114, no. 23 (2009): 4813–22. http://dx.doi.org/10.1182/blood-2009-06-226290.

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Abstract The molecular mechanisms that regulate the balance between proliferation and differentiation of precursors at the onset of hematopoiesis specification are poorly understood. By using a global gene expression profiling approach during the course of embryonic stem cell differentiation, we identified Sox7 as a potential candidate gene involved in the regulation of blood lineage formation from the mesoderm germ layer. In the present study, we show that Sox7 is transiently expressed in mesodermal precursors as they undergo specification to the hematopoietic program. Sox7 knockdown in vitro
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Gu, Yi, Michael C. Byrne, Nivanka C. Paranavitana, et al. "Rac2, a Hematopoiesis-Specific Rho GTPase, Specifically Regulates Mast Cell Protease Gene Expression in Bone Marrow-Derived Mast Cells." Molecular and Cellular Biology 22, no. 21 (2002): 7645–57. http://dx.doi.org/10.1128/mcb.22.21.7645-7657.2002.

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ABSTRACT Rho family GTPases activate intracellular kinase cascades to modulate transcription of multiple genes. Previous studies have examined the roles of the ubiquitously expressed Rho GTPase, Rac1, in regulation of gene expression in cell lines and implicated NF-κB, serum response factor, and kinase signaling pathways in this regulation. To understand the role of the closely related but hematopoiesis-specific Rho GTPase, Rac2, in regulation of gene transcription, we compared the gene expression profiles between wild-type and Rac2−/− bone marrow-derived mast cells. Our data demonstrate remar
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Liao, Eric C., Nikolaus S. Trede, David Ransom, Augustin Zapata, Mark Kieran, and Leonard I. Zon. "Non-cell autonomous requirement for thebloodlessgene in primitive hematopoiesis of zebrafish." Development 129, no. 3 (2002): 649–59. http://dx.doi.org/10.1242/dev.129.3.649.

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Vertebrate hematopoiesis occurs in two distinct phases, primitive (embryonic) and definitive (adult). Genes that are required specifically for the definitive program, or for both phases of hematopoiesis, have been described. However, a specific regulator of primitive hematopoiesis has yet to be reported. The zebrafish bloodless (bls) mutation causes absence of embryonic erythrocytes in a dominant but incompletely penetrant manner. Primitive macrophages appear to develop normally in bls mutants. Although the thymic epithelium forms normally in bls mutants, lymphoid precursors are absent. Noneth
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Contreras, Jorge R., Thilini Fernando, Tiffany M. Tran, et al. "Molecular Characterization of Long Non-Coding RNA CASC15 in Leukemogenesis." Blood 128, no. 22 (2016): 5103. http://dx.doi.org/10.1182/blood.v128.22.5103.5103.

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Abstract High throughput transcriptome sequencing has uncovered a previously uncharacterized layer of gene regulation by long non-coding RNAs (lncRNAs). LncRNAs are characterized by capped, polyadenylated, and spliced transcripts that lack an open reading frame. Despite the similarities in their genetic organization, they play variety of roles at the cellular level, including regulation of transcription and translation, leading to alterations in gene expression. One of these functions is the regulation of expression of chromosomally adjacent genes. Here, we examined the function of the lncRNA
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Guo, Fukun, Wei Liu, Kankana Chava, et al. "Role of mTOR in Hematopoiesis and Hematopoietic Stem Cell Regulation." Blood 114, no. 22 (2009): 1490. http://dx.doi.org/10.1182/blood.v114.22.1490.1490.

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Abstract Abstract 1490 Poster Board I-513 The mammalian target of rapamycin (mTOR) integrates nutrients, growth factors, and cellular energy status to control protein synthesis that determines cell growth and metabolism. It is also known that mTOR plays an essential role in cell survival by regulating Akt/PKB signaling. By using the inhibitor rapamycin, mTOR has previously been suggested to regulate proliferation of megakaryocyte progenitors and late stage of megakaryocyte differentiation without a general impact on normal hematopoiesis or hematopoietic stem cell (HSC) function. Due to limitat
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SAHA, Nirmalya, James Ropa, Lili Chen, et al. "The PAF1c Subunit Cdc73 Is Essential for Hematopoiesis and Displays Differential Gene Regulation in MLL-AF9 Driven Leukemia." Blood 132, Supplement 1 (2018): 1280. http://dx.doi.org/10.1182/blood-2018-99-118703.

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Abstract The Polymerase Associated Factor 1 complex (PAF1c) functions at the interface of epigenetics and gene transcription. The PAF1c is a multi-protein complex composed of Paf1, Cdc73, Leo1, Ctr9, Rtf1 and WDR61, which have all been shown to play a role in disease progression and different types of cancer. Previous reports demonstrated that the PAF1c is required for MLL-fusion driven acute myeloid leukemia. This is due, in part, to a direct interaction between the PAF1c and wild type MLL or MLL fusion proteins. Importantly, targeted disruption of the PAF1c-MLL interaction impairs the growth
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He, XY, VP Antao, D. Basila, JC Marx, and BR Davis. "Isolation and molecular characterization of the human CD34 gene." Blood 79, no. 9 (1992): 2296–302. http://dx.doi.org/10.1182/blood.v79.9.2296.2296.

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Abstract The human CD34 surface antigen is selectively expressed on hematopoietic stem/progenitor cells, suggesting that it plays an essential role in early hematopoiesis. Using a 1.5-kb partial human CD34 cDNA sequence, RNA-polymerase chain reaction (PCR), and rapid amplification of cDNA ends (RACE) methods, we cloned and sequenced the full-length (2.65 kb) cDNA. The cDNA encodes a type I transmembrane protein with no obvious homology to other known proteins. The entire CD34 gene of 28 kb was cloned, and the coding sequences mapped to eight exons. Mapping of the 5′ termini of mRNAs by 5′-RACE
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He, XY, VP Antao, D. Basila, JC Marx, and BR Davis. "Isolation and molecular characterization of the human CD34 gene." Blood 79, no. 9 (1992): 2296–302. http://dx.doi.org/10.1182/blood.v79.9.2296.bloodjournal7992296.

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The human CD34 surface antigen is selectively expressed on hematopoietic stem/progenitor cells, suggesting that it plays an essential role in early hematopoiesis. Using a 1.5-kb partial human CD34 cDNA sequence, RNA-polymerase chain reaction (PCR), and rapid amplification of cDNA ends (RACE) methods, we cloned and sequenced the full-length (2.65 kb) cDNA. The cDNA encodes a type I transmembrane protein with no obvious homology to other known proteins. The entire CD34 gene of 28 kb was cloned, and the coding sequences mapped to eight exons. Mapping of the 5′ termini of mRNAs by 5′-RACE and RNAa
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Huang, Mengling, Abrar Ahmed, Wei Wang, et al. "Negative Elongation Factor (NELF) Inhibits Premature Granulocytic Development in Zebrafish." International Journal of Molecular Sciences 23, no. 7 (2022): 3833. http://dx.doi.org/10.3390/ijms23073833.

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Gene expression is tightly regulated during hematopoiesis. Recent studies have suggested that RNA polymerase II (Pol II) promoter proximal pausing, a temporary stalling downstream of the promoter region after initiation, plays a critical role in regulating the expression of various genes in metazoans. However, the function of proximal pausing in hematopoietic gene regulation remains largely unknown. The negative elongation factor (NELF) complex is a key factor important for this proximal pausing. Previous studies have suggested that NELF regulates granulocytic differentiation in vitro, but its
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13

Fuller, John F., Jeanne McAdara, Yifah Yaron, Mark Sakaguchi, John K. Fraser, and Judith C. Gasson. "Characterization of HOX Gene Expression During Myelopoiesis: Role of HOX A5 in Lineage Commitment and Maturation." Blood 93, no. 10 (1999): 3391–400. http://dx.doi.org/10.1182/blood.v93.10.3391.410k26_3391_3400.

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During the process of normal hematopoiesis, proliferation is tightly linked to maturation. The molecular mechanisms that lead to production of mature effector cells with a variety of phenotypes and functions from a single multipotent progenitor are only beginning to be elucidated. It is important to determine how these maturation events are regulated at the molecular level, because this will provide significant insights into the process of normal hematopoiesis as well as leukemogenesis. Transcription factors containing the highly conserved homeobox motif show considerable promise as potential
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14

Zhaojun, Zhang, Xiong Qian, Wang Shaobin, et al. "Comprehensive Investigation of the Molecular Mechanism of Primitive Hematopoiesis Regulating by KLF3." Blood 120, no. 21 (2012): 4729. http://dx.doi.org/10.1182/blood.v120.21.4729.4729.

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Abstract Abstract 4729 KLF3 is a member of the Krüppel-like transcription factor family. By recognizing CC/ACACCC motifs in the promoters and enhancers of its regulating genes, KLF3 plays critical roles in cell differentiation and development including B lymphocytes maturation and adipocyte differentiation. Previous studies demonstrated that KLF3-deficient mice displayed myeloproliferative disorders and abnormalities in hematopoiesis. KLF3 prefers to bind to the CACCC box in the yolk sac and fetal liver, indicating that KLF3 probably participates in the primitive hematopoiesis. However, the m
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15

Inoue, Hirofumi, Ikuo Nobuhisa, Keisuke Okita, Makiko Takizawa, Marie-Josèphe Pébusque, and Tetsuya Taga. "Negative regulation of hematopoiesis by the fused in myeloproliferative disorders gene product." Biochemical and Biophysical Research Communications 313, no. 1 (2004): 125–28. http://dx.doi.org/10.1016/j.bbrc.2003.11.097.

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16

Grech, Godfrey, and Marieke von Lindern. "The Role of Translation Initiation Regulation in Haematopoiesis." Comparative and Functional Genomics 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/576540.

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Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how
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17

Sugiyama, Daisuke, Tomoko Inoue-Yokoo, Stuart T. Fraser, Kasem Kulkeaw, Chiyo Mizuochi, and Yuka Horio. "Embryonic Regulation of the Mouse Hematopoietic Niche." Scientific World JOURNAL 11 (2011): 1770–80. http://dx.doi.org/10.1100/2011/598097.

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Hematopoietic stem cells (HSCs) can differentiate into several types of hematopoietic cells (HCs) (such as erythrocytes, megakaryocytes, lymphocytes, neutrophils, or macrophages) and also undergo self-renewal to sustain hematopoiesis throughout an organism's lifetime. HSCs are currently used clinically as transplantation therapy in regenerative medicine and are typically obtained from healthy donors or cord blood. However, problems remain in HSC transplantation, such as shortage of cells, donor risks, rejection, and graft-versus-host disease (GVHD). Thus, increased understanding of HSC regulat
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18

Zambidis, Elias T., Bruno Peault, Tea Soon Park, Fred Bunz, and Curt I. Civin. "Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development." Blood 106, no. 3 (2005): 860–70. http://dx.doi.org/10.1182/blood-2004-11-4522.

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AbstractWe elucidate the cellular and molecular kinetics of the stepwise differentiation of human embryonic stem cells (hESCs) to primitive and definitive erythromyelopoiesis from human embryoid bodies (hEBs) in serum-free clonogenic assays. Hematopoiesis initiates from CD45 hEB cells with emergence of semiadherent mesodermal-hematoendothelial (MHE) colonies that can generate endothelium and form organized, yolk sac–like structures that secondarily generate multipotent primitive hematopoietic stem progenitor cells (HSPCs), erythroblasts, and CD13+CD45+ macrophages. A first wave of hematopoiesi
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19

Duan, Zhijun, Richard E. Person, Hu-Hui Lee, et al. "Epigenetic Regulation of Protein-Coding and MicroRNA Genes by the Gfi1-Interacting Tumor Suppressor PRDM5." Molecular and Cellular Biology 27, no. 19 (2007): 6889–902. http://dx.doi.org/10.1128/mcb.00762-07.

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ABSTRACT Gfi1 transcriptionally governs hematopoiesis, and its mutations produce neutropenia. In an effort to identify Gfi1-interacting proteins and also to generate new candidate genes causing neutropenia, we performed a yeast two-hybrid screen with Gfi1. Among other Gfi1-interacting proteins, we identified a previously uncharacterized member of the PR domain-containing family of tumor suppressors, PRDM5. PRDM5 has 16 zinc fingers, and we show that it acts as a sequence-specific, DNA binding transcription factor that targets hematopoiesis-associated protein-coding and microRNA genes, includin
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20

Basu, Sreemanti, Irene Hernandez, Mark Zogg, Karen-Sue B. Carlson, and Hartmut Weiler. "Regulation of Hematopoiesis By the Coagulation Receptor Thrombomodulin." Blood 126, no. 23 (2015): 4750. http://dx.doi.org/10.1182/blood.v126.23.4750.4750.

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Abstract BACKGROUND: Pharmacologic supplementation of protein C pathway function by infusion of recombinant Thbd or activated protein C supports recovery of hematopoietic function from lethal radiation injury in mice [Geiger et al., Nature Medicine, 2012]. Partial Thbd deficiency in hematopoietic stem and progenitor cells (HSPC) or bone marrow endothelium results in augmented sensitivity towards radiation injury [Geiger et al., Nature Medicine, 2012]. The underlying cellular and molecular mechanisms of Thbd function in hematopoiesis are not yet characterized. The objective of the current study
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Kwan, Tommy T., Raymond Liang, Catherine M. Verfaillie, et al. "Regulation of primitive hematopoiesis in zebrafish embryos by the death receptor gene." Experimental Hematology 34, no. 1 (2006): 27–34. http://dx.doi.org/10.1016/j.exphem.2005.09.017.

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Sato, Tomohiko, Susumu Goyama та Mineo Kurokawa. "Evi-1 Promotes Para-Aortic Splanchnopleural Hematopoiesis through Up-Regulation of GATA-2 and Repression of TGF-β Signaling." Blood 110, № 11 (2007): 1236. http://dx.doi.org/10.1182/blood.v110.11.1236.1236.

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Abstract The ecotropic viral integration site-1 (Evi-1) gene was first identified as a common locus of retroviral integration in myeloid tumors in mice. Evi-1 is highly expressed in cases with human acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) as a consequence of chromosomal rearrangements involving 3q26, where Evi-1 is mapped. Mice deficient in Evi-1 die during embryogenesis with widespread hypocellularity, hemorrhaging, and disruption in the development of the heart, somite, and neural crest-derived cells. It was recently reported that Evi-1 is expressed at a high level in
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Okoye-Okafor, Ujunwa Cynthia, Laura Barreyro, Heng Rui Wang, et al. "Molecular and Functional Characterization Of The Novel Protein-Coding Gene Tihl (Translocated in Hodgkin’s Lymphoma) in Hematopoiesis." Blood 122, no. 21 (2013): 3680. http://dx.doi.org/10.1182/blood.v122.21.3680.3680.

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Abstract Cell cycling is a tightly regulated process involving the structured expression modulation of various regulatory genes. This process is crucial for the maintenance of cell survival/proliferation in both normal and malignant hematopoietic cells. We have previously described the highly expressed CIITA-BX648577 gene fusion (Steidl C. et al., Nature 2011), involving the novel gene locus BX648577/FLJ27352 /hypothetical LOC 145788/C15orf65 and the Class II Transactivator (CIITA) in the Hodgkin’s lymphoma cell line KM-H2. While CIITA is well known to be involved in the regulation of immune r
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Nagel, Stefan. "The Role of NKL Homeobox Genes in T-Cell Malignancies." Biomedicines 9, no. 11 (2021): 1676. http://dx.doi.org/10.3390/biomedicines9111676.

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Homeobox genes encode transcription factors controlling basic developmental processes. The homeodomain is encoded by the homeobox and mediates sequence-specific DNA binding and interaction with cofactors, thus operating as a basic regulatory platform. Similarities in their homeobox sequences serve to arrange these genes in classes and subclasses, including NKL homeobox genes. In accordance with their normal functions, deregulated homeobox genes contribute to carcinogenesis along with hematopoietic malignancies. We have recently described the physiological expression of eleven NKL homeobox gene
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Raaijmakers, Marc HGP, Siddhartha Mukherjee, Shangqin Guo, et al. "Niche Induced Myelodysplasia and Secondary Hematopoietic Neoplasia Caused by Deletion of Dicer1 in Osteoprogenitor Cells." Blood 114, no. 22 (2009): 247. http://dx.doi.org/10.1182/blood.v114.22.247.247.

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Abstract Abstract 247 Introduction: Mesenchymal cells are a part of virtually every tissue in metazoans and are thought to participate in organ formation and homeostasis. In the hematopoietic system, mesenchymal cells of the osteoblast lineage have revealed their role as regulators of normal stem cell and hematopoietic physiology. Whether these cells, which have been relegated a relatively non-descript role of ‘stroma', participate in processes that result in disease is relatively understudied. Methods: To explore this, we conditionally deleted Dicer1, the endonuclease essential for miRNA biog
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Conserva, Maria Rosa, Immacolata Redavid, Luisa Anelli, et al. "IKAROS in Acute Leukemia: A Positive Influencer or a Mean Hater?" International Journal of Molecular Sciences 24, no. 4 (2023): 3282. http://dx.doi.org/10.3390/ijms24043282.

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One key process that controls leukemogenesis is the regulation of oncogenic gene expression by transcription factors acting as tumor suppressors. Understanding this intricate mechanism is crucial to elucidating leukemia pathophysiology and discovering new targeted treatments. In this review, we make a brief overview of the physiological role of IKAROS and the molecular pathway that contributes to acute leukemia pathogenesis through IKZF1 gene lesions. IKAROS is a zinc finger transcription factor of the Krüppel family that acts as the main character during hematopoiesis and leukemogenesis. It c
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Nagel, Stefan, Stefan Ehrentraut, Corinna Meyer, Maren Kaufmann, Hans G. Drexler, and Roderick AF MacLeod. "NKL Homeobox Gene MSX1 Reactivates An Oncogenic Network In Lymphoid and Myeloid Malignancies." Blood 122, no. 21 (2013): 3765. http://dx.doi.org/10.1182/blood.v122.21.3765.3765.

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Abstract Homeobox genes encode conserved transcription factors (TFs) which regulate fundamental cellular processes during development. Many members of the NKL homeobox gene subfamily are aberrantly expressed in T-cell leukemia and compromise cell differentiation. NKL homeobox gene MSX1 is expressed during embryonic hematopoiesis and its deregulation in Hodgkin lymphoma suggests an oncogenic role of this gene in hematopoietic malignancies. After screening 114 leukemia/lymphoma cell lines by microarray profiling, we detected MSX1 overexpression in three examples each from T-cell acute lymphoblas
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Hung, Chun-Hao, Keh-Yang Wang, Yae-Huei Liou, et al. "Negative Regulation of the Differentiation of Flk2− CD34− LSK Hematopoietic Stem Cells by EKLF/KLF1." International Journal of Molecular Sciences 21, no. 22 (2020): 8448. http://dx.doi.org/10.3390/ijms21228448.

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Erythroid Krüppel-like factor (EKLF/KLF1) was identified initially as a critical erythroid-specific transcription factor and was later found to be also expressed in other types of hematopoietic cells, including megakaryocytes and several progenitors. In this study, we have examined the regulatory effects of EKLF on hematopoiesis by comparative analysis of E14.5 fetal livers from wild-type and Eklf gene knockout (KO) mouse embryos. Depletion of EKLF expression greatly changes the populations of different types of hematopoietic cells, including, unexpectedly, the long-term hematopoietic stem cel
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Engel, Michael E., Hong N. Nguyen, Jolene Mariotti, Aubrey Hunt, and Scott W. Hiebert. "Myeloid Translocation Gene 16 (MTG16) Interacts with Notch Transcription Complex Components To Integrate Notch Signaling in Hematopoietic Cell Fate Specification." Molecular and Cellular Biology 30, no. 7 (2010): 1852–63. http://dx.doi.org/10.1128/mcb.01342-09.

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ABSTRACT The Notch signaling pathway regulates gene expression programs to influence the specification of cell fate in diverse tissues. In response to ligand binding, the intracellular domain of the Notch receptor is cleaved by the γ-secretase complex and then translocates to the nucleus. There, it binds the transcriptional repressor CSL, triggering its conversion to an activator of Notch target gene expression. The events that control this conversion are poorly understood. We show that the transcriptional corepressor, MTG16, interacts with both CSL and the intracellular domains of Notch recep
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Galloway, Jenna L., Christine Thisse, Yi Zhou, Rosanna Beltre, Bernard Thisse, and Leonard I. Zon. "Conversion of Erythropoiesis to Myelopoiesis in Gata1-Deficient Zebrafish Embryos." Blood 104, no. 11 (2004): 2774. http://dx.doi.org/10.1182/blood.v104.11.2774.2774.

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Abstract Primitive hematopoiesis in vertebrates initiates in the embryonic yolk sac and yields nucleated erythrocytes and macrophages that later enter circulation. In zebrafish, a group of blood cells contained within the axial vein make up the intermediate cell mass (ICM), the teleost equivalent of the mammalian yolk sac. To identify novel genes involved in hematopoiesis, a high-throughput whole embryo in situ hybridization screen was performed. Examination of the expression pattern of 3700 clones from an adult zebrafish hematopoietic cDNA library discovered 24 genes with expression in the bl
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Jonsson, JI, Q. Wu, K. Nilsson, and RA Phillips. "Use of a promoter-trap retrovirus to identify and isolate genes involved in differentiation of a myeloid progenitor cell line in vitro." Blood 87, no. 5 (1996): 1771–79. http://dx.doi.org/10.1182/blood.v87.5.1771.1771.

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Abstract Studies of gene regulation during early hematopoiesis and of the regulatory network that controls differentiation and lineage commitment are hampered by difficulties in isolating and growing stem cells and early progenitor cells. These difficulties preclude the application of standard molecular genetic approaches to these problems. As an alternative approach we have introduced a lacZ-containing promoter-trap retrovirus into hematopoietic cells. We used the interleukin-3- dependent mouse myeloid progenitor cell 32D as a model to identify transcriptionally active genes. The frequency of
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Jonsson, JI, Q. Wu, K. Nilsson, and RA Phillips. "Use of a promoter-trap retrovirus to identify and isolate genes involved in differentiation of a myeloid progenitor cell line in vitro." Blood 87, no. 5 (1996): 1771–79. http://dx.doi.org/10.1182/blood.v87.5.1771.bloodjournal8751771.

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Studies of gene regulation during early hematopoiesis and of the regulatory network that controls differentiation and lineage commitment are hampered by difficulties in isolating and growing stem cells and early progenitor cells. These difficulties preclude the application of standard molecular genetic approaches to these problems. As an alternative approach we have introduced a lacZ-containing promoter-trap retrovirus into hematopoietic cells. We used the interleukin-3- dependent mouse myeloid progenitor cell 32D as a model to identify transcriptionally active genes. The frequency of integrat
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33

Weiss, Mitchell J. "Role of Long Coding RNAs in Epigenetic Modulation of Hematopoiesis." Blood 122, no. 21 (2013): SCI—28—SCI—28. http://dx.doi.org/10.1182/blood.v122.21.sci-28.sci-28.

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Abstract Long noncoding (Lnc) RNAs are RNA transcripts greater than 200 nucleotides (nt) that regulate gene expression independent of protein coding potential (1-3). It is estimated that thousands of lncRNAs play vital roles in diverse cellular processes. LncRNAs modulate many stages of gene expression by regulating transcription, epigenetics, splicing, translation, and protein localization. We hypothesize that multiple lncRNAs are expressed specifically during erythrocyte and megakaryocyte differentiation, and are likely to have important roles. To identify lncRNAs in erythro-megakaryopoiesis
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Collins, Emma C., Alexandre Appert, Linda Ariza-McNaughton, Richard Pannell, Yoshihiro Yamada, and Terence H. Rabbitts. "Mouse Af9 Is a Controller of Embryo Patterning, Like Mll, Whose Human Homologue Fuses with AF9 after Chromosomal Translocation in Leukemia." Molecular and Cellular Biology 22, no. 20 (2002): 7313–24. http://dx.doi.org/10.1128/mcb.22.20.7313-7324.2002.

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ABSTRACT Chromosomal translocation t(9;11)(p22;q23) in acute myeloid leukemia fuses the MLL and AF9 genes. We have inactivated the murine homologue of AF9 to elucidate its normal role. No effect on hematopoiesis was observed in mice with a null mutation of Af9. However, an Af9 null mutation caused perinatal lethality, and homozygous mice exhibited anomalies of the axial skeleton. Both the cervical and thoracic regions were affected by anterior homeotic transformation. Strikingly, mice lacking functional Af9 exhibited a grossly deformed atlas and an extra cervical vertebra. To determine the mol
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Kramarzova, Karolina, Harry Drabkin, Jan Zuna, et al. "Transcription Regulation of HOX Genes in Normal Hematopoiesis and Leukemogenesis in Children." Blood 120, no. 21 (2012): 4614. http://dx.doi.org/10.1182/blood.v120.21.4614.4614.

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Abstract Abstract 4614 Introduction: The homeodomain genes (HOX genes) encode a family of highly conserved transcription factors that play fundamental roles during embryogenesis. HOX genes are also important regulators in hematopoiesis. In leukemogenesis, dysregulated expression of HOX genes has been found. Despite many correlative studies, the mechanism of establishment of leukemia specific HOX gene expression patterns in hematopoietic cells remains to be elucidated. Histone methylases and demethylases (Trithorax (TrxG), JMJD3 and Polycomb-group (PcG) genes) are chromatin modifiers regulating
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Yang, Shangda, Guohuan Sun, Peng Wu, et al. "A Novel Lncrna, Lncery, Interacts with Wdr82 to Regulate Erythroid Differentiation By Promoting Globin Gene Transcription." Blood 136, Supplement 1 (2020): 2. http://dx.doi.org/10.1182/blood-2020-139258.

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Hematopoietic differentiation is controlled by both genetic and epigenetic regulators. Long non-coding RNAs (lncRNAs) have been demonstrated to be important for normal hematopoiesis, but their function in erythropoiesis needs to be further explored. Here, we profiled the transcriptome of 17 murine hematopoietic cell populations by deep sequencing and identified a novel lncRNA, that was highly expressed in erythroid-related progenitors and erythrocytes. For this reason, we named it lncEry. We also identified a novel lncEry isoform, which was the principal transcript and has not been reported be
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Levantini, Elena, Francesca Bertolotti, Francesco Cerisoli, et al. "New Role of the Regulatory Gene SOX2 in Hematopoiesis." Blood 104, no. 11 (2004): 4195. http://dx.doi.org/10.1182/blood.v104.11.4195.4195.

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Abstract Several genes encoding transcription factors of different families have been implicated in the development and differentiation of multiple cell systems. The Sry-type high-mobility-group box 2 gene (Sox2) encodes a transcription factor that is expressed in very early cells such as embryonic stem cells and neural stem cells, where it plays important functional roles (Genes and Dev.17:126, 2003; Development131:3805, 2004). To investigate whether Sox2 plays a role also in blood cell production, we first analyzed its expression in murine hematopoietic cells. Results indicate that the gene
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Sattler, Martin, Shalini Verma, Christopher H. Byrne, et al. "BCR/ABL Directly Inhibits Expression of SHIP, an SH2-Containing Polyinositol-5-Phosphatase Involved in the Regulation of Hematopoiesis." Molecular and Cellular Biology 19, no. 11 (1999): 7473–80. http://dx.doi.org/10.1128/mcb.19.11.7473.

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ABSTRACT The BCR/ABL oncogene causes chronic myelogenous leukemia (CML), a myeloproliferative disorder characterized by clonal expansion of hematopoietic progenitor cells and granulocyte lineage cells. The SH2-containing inositol-5-phosphatase SHIP is a 145-kDa protein which has been shown to regulate hematopoiesis in mice. Targeted disruption of the murine SHIP gene results in a myeloproliferative syndrome characterized by a dramatic increase in numbers of granulocyte-macrophage progenitor cells in the marrow and spleen. Also, hematopoietic progenitor cells from SHIP−/−mice are hyperresponsiv
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39

Gao, Hongjuan, Xiaorong Wu, and Nancy Fossett. "Upregulation of the Drosophila Friend of GATA Gene u-shaped by JAK/STAT Signaling Maintains Lymph Gland Prohemocyte Potency." Molecular and Cellular Biology 29, no. 22 (2009): 6086–96. http://dx.doi.org/10.1128/mcb.00244-09.

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ABSTRACT Studies using Drosophila melanogaster have contributed significantly to our understanding of the interaction between stem cells and their protective microenvironments or stem cell niches. During lymph gland hematopoiesis, the Drosophila posterior signaling center functions as a stem cell niche to maintain prohemocyte multipotency through Hedgehog and JAK/STAT signaling. In this study, we provide evidence that the Friend of GATA protein U-shaped is an important regulator of lymph gland prohemocyte potency and differentiation. U-shaped expression was determined to be upregulated in thir
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Trombetti, Silvia, Nunzia Iaccarino, Patrizia Riccio, et al. "Over-Expressed GATA-1S, the Short Isoform of the Hematopoietic Transcriptional Factor GATA-1, Inhibits Ferroptosis in K562 Myeloid Leukemia Cells by Preventing Lipid Peroxidation." Antioxidants 12, no. 3 (2023): 537. http://dx.doi.org/10.3390/antiox12030537.

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Ferroptosis is a recently recognized form of regulated cell death involving lipid peroxidation. Glutathione peroxidase 4 (GPX4) plays a central role in the regulation of ferroptosis through the suppression of lipid peroxidation generation. Connections have been reported between ferroptosis, lipid metabolism, cancer onset, and drug resistance. Recently, interest has grown in ferroptosis induction as a potential strategy to overcome drug resistance in hematological malignancies. GATA-1 is a key transcriptional factor controlling hematopoiesis-related gene expression. Two GATA-1 isoforms, the ful
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Li, Feng X., Jing W. Zhu, Christopher J. Hogan, and James DeGregori. "Defective Gene Expression, S Phase Progression, and Maturation during Hematopoiesis in E2F1/E2F2 Mutant Mice." Molecular and Cellular Biology 23, no. 10 (2003): 3607–22. http://dx.doi.org/10.1128/mcb.23.10.3607-3622.2003.

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ABSTRACT E2F plays critical roles in cell cycle progression by regulating the expression of genes involved in nucleotide synthesis, DNA replication, and cell cycle control. We show that the combined loss of E2F1 and E2F2 in mice leads to profound cell-autonomous defects in the hematopoietic development of multiple cell lineages. E2F2 mutant mice show erythroid maturation defects that are comparable with those observed in patients with megaloblastic anemia. Importantly, hematopoietic defects observed in E2F1/E2F2 double-knockout (DKO) mice appear to result from impeded S phase progression in he
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Tarrant, Jacqueline M., Joanna Groom, Donald Metcalf, et al. "The Absence of Tssc6, a Member of the Tetraspanin Superfamily, Does Not Affect Lymphoid Development but Enhances In Vitro T-Cell Proliferative Responses." Molecular and Cellular Biology 22, no. 14 (2002): 5006–18. http://dx.doi.org/10.1128/mcb.22.14.5006-5018.2002.

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ABSTRACT The tetraspanins are a family of integral membrane proteins with four transmembrane domains. These molecules form multimolecular networks on the surfaces of many different cell types. Gene-targeting studies have revealed a role for tetraspanins in B- and T-lymphocyte function. We have isolated and deleted a novel tetraspanin, Tssc6, which is expressed exclusively in hematopoietic and lymphoid organs. Using a gene-trapping strategy, we generated an embryonic stem (ES) cell line with an insertion in the Tssc6 locus. Mice were derived from these ES cells and, using RNase protection and r
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43

Yang, Yu-Chung, and Steven C. Clark. "Human interleukin 3: Analysis of the gene and its role in the regulation of hematopoiesis." International Journal of Cell Cloning 8, S1 (1990): 121–29. http://dx.doi.org/10.1002/stem.5530080711.

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Staeble, Sina, Stephen Kraemer, Jens Langstein, et al. "Deconvolution of Hematopoietic Commitment Decisions By Genome-Wide Analysis of Progressive DNA Methylation Changes." Blood 134, Supplement_1 (2019): 1179. http://dx.doi.org/10.1182/blood-2019-124429.

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Recent advances in single cell transcriptome analyses have resulted in the derivation of new models to describe the hierarchical organization of the mammalian hematopoietic system. While such an approach appears to be effective at discerning the trajectory of differentiation from hematopoietic stem cells (HSCs) to a given mature lineage, it remains a challenge to identify definitive points where specific lineage fates become restricted. The characterization of molecular events that correspond to such commitment decisions is critical to our interrogation of the existence and nature of serial bi
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de Alava, Enrique, and William L. Gerald. "Molecular Biology of the Ewing’s Sarcoma/Primitive Neuroectodermal Tumor Family." Journal of Clinical Oncology 18, no. 1 (2000): 204. http://dx.doi.org/10.1200/jco.2000.18.1.204.

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ABSTRACT: Ewing’s sarcoma (ES) and primitive neuroectodermal tumor (PNET) are members of a tumor family consistently associated with chromosomal translocation and functional fusion of the EWS gene to any of several structurally related transcription factor genes. Similar gene fusion events occur in other mesenchymal and hematopoietic tumors and are tumor-specific. The resulting novel transcription factor–like chimeric proteins are believed to contribute to tumor biology by aberrant regulation of gene expression altering critical controls of cell proliferation and differentiation. These tumor-s
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Andina, Nicola Daniele, Mayuresh Sarangdhar, Aubry Tardivel, et al. "Higher Vertebrate Specific Gene Ribonuclease Inhibitor (RNH1) Is Essential for Adult Hematopoietic Stem Cell Function and Cell Cycle Regulation." Blood 134, Supplement_1 (2019): 273. http://dx.doi.org/10.1182/blood-2019-128647.

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Hematopoietic stem cells (HSC) in higher vertebrate species, especially in mammals, maintain hematopoiesis throughout adult life and require critical cell cycle regulation for their self-renewal and cell fate decisions. Although cell cycle pathways are quite conserved across animal species, it is unknown whether a higher vertebrate specific cell cycle regulation exists in adult mammalian HSCs. Recently, we have published that Ribonuclease inhibitor (RNH1) regulates erythropoiesis by controlling GATA1 mRNA translation. Here, we report that RNH1, which is present only in higher vertebrates regul
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Raman, Rachna, Ashwini Hinge, Rupali Kumar, Juying Xu, Kathleen Szczur, and Marie-Dominique Filippi. "P190-B RhoGAP Is Critical for Hematopoietic Stem Cell Niche Regulation." Blood 118, no. 21 (2011): 221. http://dx.doi.org/10.1182/blood.v118.21.221.221.

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Abstract Abstract 221 Hematopoiesis is regulated by components of the stromal microenvironment, so-called niche. Although the concept of hematopoietic stem and progenitor cell (HSC/P) niche is well known, its molecular regulation remains ill-defined. Here, we provide evidence that p190-B GTPase Activating Protein (p190-B), a negative regulator of Rho activity, is a regulator of mesenchymal/stromal cell functions necessary for normal hematopoiesis during fetal development. Mice lacking p190-B die before birth. At day 14.5 post coitum, p190-B−/− embryos are paler than WT embryos with a 40% lower
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Xiong, Qian, Zhaojun Zhang, Hongzhu Qu, et al. "Deciphering the Cis- and Trans-regulatory Roles of KLF6 in Primitive Hematopoiesis." Blood 120, no. 21 (2012): 4730. http://dx.doi.org/10.1182/blood.v120.21.4730.4730.

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Abstract Abstract 4730 Krüppel-like factors (KLFs) are a conserved family of Cys2His2 zinc finger proteins which are important components of eukaryotic cellular transcriptional machinery that controls many biological processes including erythroid differentiation and development. As a transcriptional activator and a tumor suppressor, KLF6 was also involved in hematopoiesis. Klf6−/− mice is embryonic lethal by embryonic day 12.5 and associated with markedly reduced hematopoiesis as well as poorly organized yolk sac vascularization. Moreover, the expression of erythroid differentiation markers i
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Konantz, Martina, Sarah Grzywna, Tamara C. Pereboom, et al. "Multiple Roles for the Zebrafish Homologue of the Murine Evi1 Gene during Primitive Myelopoiesis and HSC Development." Blood 124, no. 21 (2014): 2901. http://dx.doi.org/10.1182/blood.v124.21.2901.2901.

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Abstract The Evi1 locus was originally identified as a common site of retroviral integration in murine myeloid tumors. Several reports associate Evi1 expression with aggressiveness in myeloid leukemia. Since developmental pathways often reactivate in cancer, we hypothesized that Evi1 also plays critical roles during developmental hematopoiesis. Here, we employ the zebrafish model to study how evi1 modulates early blood development. We find that indeed zebrafish evi1 co-localizes with the hematopoietic markers scl, gata1, pu.1 and gata2 in the posterior lateral mesoderm and the rostral blood is
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Mattiucci, Domenico, Giulia Maurizi, Pietro Leoni, and Antonella Poloni. "Aging- and Senescence-associated Changes of Mesenchymal Stromal Cells in Myelodysplastic Syndromes." Cell Transplantation 27, no. 5 (2018): 754–64. http://dx.doi.org/10.1177/0963689717745890.

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Hematopoietic stem and progenitor cells reside within the bone marrow (BM) microenvironment. By a well-balanced interplay between self-renewal and differentiation, they ensure a lifelong supply of mature blood cells. Physiologically, multiple different cell types contribute to the regulation of stem and progenitor cells in the BM microenvironment by cell-extrinsic and cell-intrinsic mechanisms. During the last decades, mesenchymal stromal cells (MSCs) have been identified as one of the main cellular components of the BM microenvironment holding an indispensable role for normal hematopoiesis. D
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