Expression and prognostic significance of hsa-miR-1423 p in acute leukemias

Objectives: The microRNA 142 (miR-142) is expressed at high levels in mature hematopoietic cells and has a crucial role during T-lymphocyte development. Its role in leukemogenesis is unclear. Patients and methods: Expression of miR-142 was analyzed in acute myeloid and lymphoblastic leukemia cells (de novo, cell lines). Data were compared to expression in CD34+ hematopoietic cells. Based on the miR-142 expression, clinical data such as overall survival was analyzed. Results: MiR-142 expression in all leukemia cell lines and 86 % of the de novo samples was higher than in CD34+ cells. This difference could be detected in both, myeloid and lymphoid neoplastic cells. In AML patients with intermediate cytogenetic risk a high miR-142 expression was associated with a better overall survival. Conclusions: MiR-142 expression in acute lymphoblastic as well as myeloid leukemia cells is higher than in CD34+ cells. Additionally, miR-142 expression might have prognostic relevance in AML-patients with otherwise an intermediate cytogenetic risk.

[1]  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.

[2]  P. Bednarski,et al.  Characterization of three B-cell lymphoma cell lines from chemotherapy resistant patients with respect to in vitro sensitivity to 21 antitumor agents, ABC-transporter expression and cellular redox status , 2007, Journal of Cancer Research and Clinical Oncology.

[3]  T. Zhu,et al.  Downregulation of microRNA-142 by proto-oncogene LMO2 and its co-factors , 2008, Leukemia.

[4]  M. D. Boer,et al.  Identification of new microRNA genes and aberrant microRNA profiles in childhood acute lymphoblastic leukemia , 2009, Leukemia.

[5]  Torsten Haferlach,et al.  Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin , 2008, Proceedings of the National Academy of Sciences.

[6]  G. Calin,et al.  The role of microRNA in human leukemia: a review , 2009, Leukemia.

[7]  T Chaplin,et al.  MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis , 2007, Leukemia.

[8]  Monika Belickova,et al.  Differential expression of microRNAs in hematopoietic cell lineages , 2008, European journal of haematology.

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

[10]  M. Biffoni,et al.  MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis , 2009, Haematologica.

[11]  M. Kelliher,et al.  The Notch1/c-Myc Pathway in T Cell Leukemia , 2007, Cell cycle.

[12]  K Wheatley,et al.  The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. , 1998, Blood.

[13]  R. C. Macridis.  A review , 1963 .

[14]  Yoshikazu Nakamura,et al.  Altered expression profiles of microRNAs during TPA-induced differentiation of HL-60 cells. , 2004, Biochemical and biophysical research communications.

[15]  Todd R. Golub,et al.  MicroRNA Expression Signatures Accurately Discriminate Acute Lymphoblastic Leukemia from Acute Myeloid Leukemia. , 2007 .

[16]  M. Pfaffl,et al.  A new mathematical model for relative quantification in real-time RT-PCR. , 2001, Nucleic acids research.

[17]  G. Horgan,et al.  Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR , 2002 .

[18]  Richard A Young,et al.  Global and Hox-specific roles for the MLL1 methyltransferase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[19]  C. Sander,et al.  A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing , 2007, Cell.

[20]  C. Croce,et al.  MiR-15a and miR-16-1 cluster functions in human leukemia , 2008, Proceedings of the National Academy of Sciences.

[21]  Grace X. Y. Zheng,et al.  Dynamic regulation of miRNA expression in ordered stages of cellular development. , 2007, Genes & development.