Karyotype-specific microRNA signature in chronic lymphocytic leukemia

Visone, Rosa; Rassenti, Laura Z.; Veronese, Angelo; Taccioli, Cristian; Costinean, Stefan; Aguda, Baltazar D.; Volinia, Stefano; Ferracin, Manuela; Palatini, Jeff; Balatti, Veronica; Alder, Hansjüerg; Negrini, Massimo; Kipps, Thomas J.; Croce, Carlo M.

doi:10.1182/blood-2009-06-229211

Cited by 178 publications

(143 citation statements)

References 44 publications

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“…Several miRNAs play important roles in hematopoiesis and their deregulation can contribute to leukemogenesis (23,(38)(39)(40)(41)(42)(43)(44). However, the mechanisms of action of only a few oncogenic miRNAs have been investigated.…”

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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“…Down-regulation of miR-146a expression by the c-Myc oncogenic transcription factor has been previously observed in human and mouse B-cell lymphomas (30). Recent studies have evaluated the expression levels of miR-146a in acute lymphocytic leukemia and chronic lymphocytic leukemia (31)(32)(33). Their findings imply that miR-146a expression involved in deletion or amplification may be cell type-specific.…”

Section: Mir-155 and Mir-146a As Diagnostic Tools In Dlbcl Patientsmentioning

confidence: 99%

Clinical and prognostic significance of miR-155 and miR-146a expression levels in formalin-fixed/paraffin-embedded tissue of patients with diffuse large B-cell lymphoma

Zhong¹,

Xu²,

Zhong³

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. It has been found that aberrant expression of microRNAs (miRNAs) is strongly associated with carcinogenesis. In the present study, we investigated the expression of miR-155 and miR-146a in diffuse large B-cell lymphoma (DLBCL) patients (n=90). The expression levels of miR-155 and miR-146a were significantly higher in de novo DLBCL patients. miR-146a expression levels were associated with miR-155, lactate dehydrogenase, β 2 microglobulin, c-myc, International Prognostic Index status and Eastern Cooperative Oncology Group performance status. We found that patients with low miR-155 and miR-146a expression levels achieved a higher complete remission rate, higher overall response rate and longer progression-free survival time. Moreover, a high expression level of miR-155, but not miR-146a, was an independent indicator for chemotherapy protocol selection in our study. Patients with high expression of miR-155 received more survival benefits from rituximab treatment. These data suggest that miR-155 and miR-146a have potential as diagnostic and prognostic markers in DLBCL.

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“…24,25 Recently, specific miRNA signatures that discriminate del(11q), del(17p), trisomy 12, del(13q) and normal karyotype cytogenetic subgroups have also been identified. 26 Despite the unquestionable importance of these markers, they need further validation before they are used on a routine basis.…”

Section: Hronic Lymphocytic Leukemia (Cll) Is a Frequent Cd5mentioning

confidence: 99%