Micro-RNA response to imatinib mesylate in patients with chronic myeloid leukemia

Micro-RNAs (miRNAs) control gene expression by destabilizing targeted transcripts and inhibiting their translation. Aberrant expression of miRNAs has been described in many human cancers, including chronic myeloid leukemia. Current first-line therapy for newly diagnosed chronic myeloid leukemia is i...

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Bibliographic Details
Published in:Haematologica (Roma) 2010-08, Vol.95 (8), p.1325-1333
Main Authors: FLAMANT, Stéphane, RITCHIE, William, GUILHOT, Joëlle, HOLST, Jeff, BONNET, Marie-Laure, CHOMEL, Jean-Claude, GUILHOT, François, TURHAN, Ali G, RASKO, John E. J
Format: Article
Language:English
Subjects:
Aged
Antineoplastic Agents - therapeutic use
Benzamides
Biological and medical sciences
Cells, Cultured
Chromosome aberrations
Female
Gene Expression Profiling
Gene Expression Regulation, Leukemic - drug effects
Hematologic and hematopoietic diseases
Humans
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Male
Medical genetics
Medical sciences
MicroRNAs - genetics
Middle Aged
Oligonucleotide Array Sequence Analysis
Original
Piperazines - therapeutic use
Pyrimidines - therapeutic use
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
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Summary:Micro-RNAs (miRNAs) control gene expression by destabilizing targeted transcripts and inhibiting their translation. Aberrant expression of miRNAs has been described in many human cancers, including chronic myeloid leukemia. Current first-line therapy for newly diagnosed chronic myeloid leukemia is imatinib mesylate, which typically produces a rapid hematologic response. However the effect of imatinib on miRNA expression in vivo has not been thoroughly examined. Using a TaqMan Low-Density Array system, we analyzed miRNA expression in blood samples from newly diagnosed chronic myeloid leukemia patients before and within the first two weeks of imatinib therapy. Quantitative real-time PCR was used to validate imatinib-modulated miRNAs in sequential primary chronic myeloid leukemia samples (n=11, plus 12 additional validation patients). Bioinformatic target gene prediction analysis was performed based on changes in miRNA expression. We observed increased expression of miR-150 and miR-146a, and reduced expression of miR-142-3p and miR-199b-5p (3-fold median change) after two weeks of imatinib therapy. A significant correlation (P
ISSN:0390-6078
1592-8721
DOI:10.3324/haematol.2009.020636