CD34, RAB20, PU.1 and GFI1 mRNA expression in myelodysplastic syndrome

Huh, Hee Jin; Chae, Seok-Lae; Lee, Mi-Ae; Hong, Kiseok; Mun, Yeung Chul; Seong, Chu-Myong; Chung, Wha Soon

doi:10.1111/j.1751-553x.2008.01056.x

Cited by 18 publications

(18 citation statements)

References 34 publications

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“…SPI1 encodes transcription factor PU.1, mediating myeloid cell development, 39 the expression of which is downregulated in particular subtypes of AML and MDS. 40,41 Taken together, our results suggest that the upregulation of miR-34a in early MDS possibly affects not only apoptosis of HSCs through BCL2 but could also decrease PU.1 expression, which in consequence may impede myeloid signaling and contribute to ineffective hematopoiesis of early MDS.…”

Section: Discussionmentioning

confidence: 68%

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

et al. 2010

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MicroRNAs (miRNAs) are small non-coding RNAs functioning as regulators of hematopoiesis. Their differential expression patterns have been linked with various pathological processes originating from hematopoietic stem cells (HSCs). However, limited information is available regarding the role of miRNAs in myelodysplastic syndrome (MDS). Using miRNA arrays, we measured expression of 1,145 miRNAs in CD34+ bone marrow cells obtained from 39 MDS and acute myeloid leukemia (AML) evolved from MDS patients, and compared them with those of six healthy donors. Differential miRNA expression was analyzed and a panel of upregulated (n¼13) and downregulated (n¼9) miRNAs were found (Po0.001) in MDS/AML patients. An increased expression of a large miRNA cluster mapped within the 14q32 locus was detected. Differences in miRNA expression of MDS subtypes showed a distinction between early and advanced MDS; an apparent dissimilarity was observed between RAEB-1 and RAEB-2 subtypes. In early MDS, we monitored upregulation of proapoptotic miR-34a, which may contribute to the increased apoptosis of HSCs. Patients with 5q deletion were characterized by decreased levels of miR-143* and miR-378 mapped within the commonly deleted region at 5q32. This is an early report describing differential expression in MDS CD34+ cells, likely reflecting their disease-specific regulation.

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Section: Discussionmentioning

confidence: 68%

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

et al. 2010

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“…Hence, only in situations where protection against apoptosis coincides with Gfi1 deficiency and thus with elevated Hoxa9 levels and myeloid expansion, a myeloproliferative-like state can emerge and possibly also further develop into a myeloid leukemia. This may also explain clinical findings that myelodysplastic patients expressing low levels of Gfi1 have an increased risk to develop leukemia [38]. Here, the balance of the different functions of Gfi1 may have been tipped to favor þ Gr1 À population detected in A.…”

Section: Bcl-2 Overexpression Causes a Myeloproliferative-like Diseasmentioning

confidence: 94%

“…In addition, a Gfi1 variant is associated with AML and, neutropenia causing mutations of Gfi1 are associated with an elevated AML risk [37][38][39][40][41]. Moreover, Gfi1-deficient mice show expanded myeloid cell populations and up-regulated levels of Hoxa9.…”

Section: Bcl-2 Overexpression Causes a Myeloproliferative-like Diseasmentioning

confidence: 99%

Growth Factor Independence 1 Protects Hematopoietic Stem Cells Against Apoptosis but Also Prevents the Development of a Myeloproliferative-Like Disease

et al. 2011

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The regulation of gene transcription is elementary for the function of hematopoietic stem cells (HSCs). The transcriptional repressor growth factor independence 1 (Gfi1) restricts HSC proliferation and is essential to maintain their self-renewal capacity and multipotency after transplantation. In addition, Gfi1−/− HSCs are severely compromised in their ability to compete with wild-type (wt) HSCs after transplantation. We now report that Gfi1 protects HSCs against stress-induced apoptosis, probably, by repressing the proapoptotic target gene Bax, since irradiated Gfi1−/− HSCs display higher expression of Bax and show a higher rate of apoptosis than wt HSCs. This protective function of Gfi1 appears to be functionally relevant since Gfi1−/− HSCs that express Bcl-2, which antagonizes the effects of Bax, regain their ability to self renew and to initiate multilineage differentiation after transplantation. Surprisingly, Gfi1−/−xBcl-2 transgenic mice also show a strong, systemic expansion of Mac-1+Gr-1− myeloid cells in bone marrow and peripheral lymphoid organs. These cells express high levels of the proleukemogenic transcription factor Hoxa9 and, in older mice, appear as atypical monocytoid-blastoid cells in the peripheral blood. As a result of this massive expansion of myeloid cells, all Gfi1−/−xBcl-2 mice eventually succumb to a myeloproliferative-like disease resembling a preleukemic state. In summary, our data demonstrate that Gfi1's ability to protect against apoptosis is essential for HSC function. In addition, our finding show that Gfi1 prevents the development of myeloproliferative diseases and provides evidence how Gfi1 deficiency could be linked to myeloid leukemia.

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“…Low expression of Gfi1 has been found in subtypes of patients with myelodysplastic syndromes. 59 In contrast, elevated expression of Gfi1 has been reported in patients with chronic myeloid leukemia, 60 and large variations of Gfi1 expression were detected in different acute myeloid leukemia subtypes. 61 It will therefore be important to study whether an aberrant Gfi1 expression contributes to the development of human myeloid malignancies.…”

Section: Gfi1mentioning

confidence: 97%

Gfi1 and Gfi1b: key regulators of hematopoiesis

2010

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Transcription factor Growth factor independence 1 (Gfi1) is required for multilineage blood cell development, from stem and progenitor cells to differentiated lymphoid and myeloid cells. Gfi1 expression is rapidly induced by cytokines that control both the adaptive and innate immune systems. Gfi1 itself represses the expression of genes implicated in cell survival, proliferation and differentiation. Changes in Gfi1 expression and function have not only been implicated in neutropenia, allergy, autoimmunity and hyperinflammatory responses, but also in lymphoma and more recently in the development of leukemia. In this study, we review how Gfi1 and its paralogue Gfi1b control the development of blood cells, discuss how changes in Gfi1 and Gfi1b function contribute to hematological disease and report on the molecular function of these proteins.

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CD34, RAB20, PU.1 and GFI1 mRNA expression in myelodysplastic syndrome

Cited by 18 publications

References 34 publications

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome

Growth Factor Independence 1 Protects Hematopoietic Stem Cells Against Apoptosis but Also Prevents the Development of a Myeloproliferative-Like Disease

Gfi1 and Gfi1b: key regulators of hematopoiesis

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