MicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors

Lü, Jun; Guo, Shangqin; Ebert, Benjamin L.; Zhang, Hao; Peng, Xiao; Bosco, J.; Pretz, Jennifer; Schlanger, Rita; Wang, Judy Y.; Mak, Raymond H.; Dombkowski, David; Preffer, Frederic I.; Scadden, David T.; Golub, Todd R.

doi:10.1016/j.devcel.2008.03.012

Cited by 311 publications

(331 citation statements)

References 40 publications

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“…In this study, we identified miR-150 as a new regulator for MLL-associated leukemia, one of the most aggressive leukemias with a poor prognosis. miR-150 is a key miRNA involved in hematopoiesis via suppression of Myb and other potential target genes (6,7,13,14,45,46). Altered expression of crucial developmental regulators is often linked with diseases and cancer transformation, so it was not surprising to observe that altered expression of miR-150 was detected in multiple hematopoietic disorders.…”

Section: Discussionmentioning

confidence: 99%

miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression

Bousquet

Zhuang

et al. 2013

Molecular Cancer Research

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The microRNA miR-150, a critical regulator of hematopoiesis, is downregulated in mixed-lineage leukemia (MLL). In this study, miR-150 acts as a potent leukemic tumor suppressor by blocking the oncogenic properties of leukemic cells. By using MLL-AF9-transformed cells, we demonstrate that ectopic expression of miR-150 inhibits blast colony formation, cell growth, and increases apoptosis in vitro. More importantly, ectopic expression of miR-150 in MLL-AF9-transformed cells completely blocked the development of myeloid leukemia in transplanted mice. Furthermore, gene expression profiling revealed that miR-150 altered the expression levels of more than 30 "stem cell signature" genes and many others that are involved in critical cancer pathways. In addition to the known miR-150 target Myb, we also identified Cbl and Egr2 as bona fide targets and shRNA-mediated suppression of these genes recapitulated the pro-apoptotic effects observed in leukemic cells with miR-150 ectopic expression.In conclusion, we demonstrate that miR-150 is a potent leukemic tumor suppressor that regulates multiple oncogenes.Implications: These data establish new, key players for the development of therapeutic strategies to treat MLL-AF9-related leukemia. Mol Cancer Res; 11(8); 912-22. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 99%

miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression

Bousquet

Zhuang

et al. 2013

Molecular Cancer Research

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“…There is growing evidence that miRNAs regulate hematopoiesis in both hematopoietic stem cells and committed progenitor cells [17][18][19][20][21][22][23][24][25]. Deregulated miRNA profiles have been reported in MPN patients during in vitro erythroid differentiation as well as in peripheral blood granulocytes, platelets, and reticulocytes [26,27].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients

Zhan

Cardozo

et al. 2013

Blood Cells, Molecules, and Diseases

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Polycythemia vera (PV) and essential thrombocythemia (ET) are the two most common myeloproliferative neoplasms. The same JAK2 V617F mutation can be found in both disorders and is able to recapitulate many of the phenotypic abnormalities of these diseases in the murine models. The disease phenotype is also influenced by other unknown genetic or epigenetic factors. MicroRNAs (miRNA) are 18-24 nucleotides single-stranded non-protein-coding RNAs that function primarily as gene repressors by binding to their target messenger RNAs. We performed miRNA expression profiling by oligonucleotide microarray analysis in purified peripheral blood CD34+ cells from eight JAK2 V617F -positive PV patients and six healthy donors. A quantitative reverse-transcription polymerase chain reaction assay was used to verify differential miRNA expression. Since erythrocytosis is the only feature that distinguishes PV from ET, we also compared specific miRNA expression in the nucleated erythroid cells directly descended from the early erythroid progenitor cells of PV and ET patients. Our data indicate that significant miRNA deregulation occurs in PV CD34+ cells and confirm a genetic basis for the gender-specific differences that characterize PV with respect to miRNA. The results of our study also suggest that deregulated miRNAs may represent an important mechanism by which the PV erythrocytosis and ET thrombocytosis phenotypes are determined.

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“…They also showed that these miRNAs downregulated mafB and HOXA-1, respectively, providing a mechanism for this biological effect. Using a novel method of miRNA profiling capable of generating a usable profile with as low as 10 ng of RNA, Lu et al 40 showed an overexpression of miR-150 in cells differentiated into the megakaryocytic lineage. Overexpression of miR-150 in megakaryocyte-erythrocyte progenitor cells led to a preferential differentiation toward the megakaryocytic lineage both in vitro and in vivo.…”

Section: Megakaryocyte Developmentmentioning

confidence: 99%

The role of microRNA in human leukemia: a review

Yendamuri

Calin

2009

Leukemia

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MicroRNAs (miRNAs or miRs) are 18-22-nucleotide non-coding RNAs that have emerged as a new paradigm of epigenetic regulation in both normal development and cellular function, and in the pathogenesis of human disease including cancer. This review summarizes the current literature of mechanism of gene regulation by miRNA and their role in hematopoiesis and leukemogenesis. An understanding of these processes suggests further avenues for research to understand gene regulation and miRNA-based therapeutic approaches.

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MicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors

Cited by 311 publications

References 40 publications

miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression

miR-150 Blocks MLL-AF9–Associated Leukemia through Oncogene Repression

MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients

The role of microRNA in human leukemia: a review

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