Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation

Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2;11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we have shown that this translocation is associated with a strong up-regulation of miR-125b (from 6- to 90-fold). In vitro experiments revealed that miR-125b was able to interfere with primary human CD34+ cell differentiation, and also inhibited terminal (monocytic and granulocytic) differentiation in HL60 and NB4 leukemic cell lines. Therefore, miR-125b up-regulation may represent a new mechanism of myeloid cell transformation, and myeloid neoplasms carrying the t(2;11) translocation define a new clinicopathological entity.

[1]  N Asou,et al.  Insertion of microRNA-125b-1, a human homologue of lin-4, into a rearranged immunoglobulin heavy chain gene locus in a patient with precursor B-cell acute lymphoblastic leukemia , 2005, Leukemia.

[2]  George A Calin,et al.  MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. , 2008, Blood.

[3]  P. Nowell,et al.  Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Gary Ruvkun,et al.  A Whole-Genome RNAi Screen for C. elegans miRNA Pathway Genes , 2007, Current Biology.

[5]  Tara L. Naylor,et al.  microRNAs exhibit high frequency genomic alterations in human cancer. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[6]  F. Lo‐Coco,et al.  Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein. , 2007, Cancer cell.

[7]  Anindya Dutta,et al.  The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. , 2007, Genes & development.

[8]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[9]  U. Hämmerling,et al.  Growth control or terminal differentiation: endogenous production and differential activities of vitamin A metabolites in HL-60 cells , 1993, The Journal of experimental medicine.

[10]  C. Croce,et al.  MicroRNA signatures in human cancers , 2006, Nature Reviews Cancer.

[11]  Kwang-Soo Kim,et al.  Depletion of Human Micro-RNA miR-125b Reveals That It Is Critical for the Proliferation of Differentiated Cells but Not for the Down-regulation of Putative Targets during Differentiation* , 2005, Journal of Biological Chemistry.

[12]  D. Bartel,et al.  MicroRNAs Modulate Hematopoietic Lineage Differentiation , 2004, Science.

[13]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  W. Crosby,et al.  Cytochemical identification of monocytes and granulocytes. , 1971, American journal of clinical pathology.

[15]  C. Croce,et al.  CD34+ hematopoietic stem-progenitor cell microRNA expression and function: A circuit diagram of differentiation control , 2006, Proceedings of the National Academy of Sciences.

[16]  Carlo M. Croce,et al.  MicroRNAs 17-5p–20a–106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation , 2007, Nature Cell Biology.

[17]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[18]  George A Calin,et al.  Chromosomal rearrangements and microRNAs: a new cancer link with clinical implications. , 2007, The Journal of clinical investigation.

[19]  Thomas D. Schmittgen,et al.  Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. , 2007, Cancer cell.

[20]  B. Kroesen,et al.  The role of microRNAs in normal hematopoiesis and hematopoietic malignancies , 2006, Leukemia.

[21]  Alessandro Fatica,et al.  A Minicircuitry Comprised of MicroRNA-223 and Transcription Factors NFI-A and C/EBPα Regulates Human Granulopoiesis , 2005, Cell.