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- Title
Identification of new microRNA genes and aberrant microRNA profiles in childhood acute lymphoblastic leukemia.
- Authors
Schotte, D.; Chau, J. C. K.; Sylvester, G.; Liu, G.; Chen, C.; van der Velden, V. H. J.; Broekhuis, M. J. C.; Peters, T. C. J. M.; Pieters, R.; den Boer, M. L.
- Abstract
MicroRNAs (miRNAs) control the expression of protein-coding genes in normal hematopoietic cells and, consequently, aberrant expression may contribute to leukemogenesis. To identify miRNAs relevant to pediatric acute lymphoblastic leukemia (ALL), we cloned 105 known and 8 new miRNA genes expressed in patients’ leukemia cells. Instead of known miRNA genes, new miRNA genes were not evolutionarily conserved. Quantification of 19 selected miRNA genes revealed an aberrant expression in ALL as compared with normal CD34+ cells (P0.02); both upregulated (14/19) and downregulated (5/19) expressions were observed. Eight miRNAs were differentially expressed between MLL and non-MLL precursor B-ALL cases (P<0.05). Most remarkably, miR-708 was 250- up to 6500-fold higher expressed in 57 TEL-AML1, BCR-ABL, E2A-PBX1, hyperdiploid and B-other cases than in 20 MLL-rearranged and 15 T-ALL cases (0.0001< P<0.01), whereas the expression of miR-196b was 500-fold higher in MLL-rearranged and 800-fold higher in 5 of 15 T-ALL cases as compared with the expression level in the remaining precursor B-ALL cases (P<0.001). The expression did not correlate with the maturation status of leukemia cells based on immunoglobulin and T-cell receptor rearrangements, immunophenotype or MLL-fusion partner. In conclusion, we identified new miRNA genes and showed that miRNA expression profiles are ALL subtype-specific rather than linked to the differentiation stadium associated with these subtypes.Leukemia (2009) 23, 313–322; doi:10.1038/leu.2008.286; published online 16 October 2008
- Subjects
RNA; LEUKEMIA etiology; LYMPHOBLASTIC leukemia in children; LEUKEMIA in children; IMMUNOGLOBULINS; CELL receptors; CHILD care
- Publication
Leukemia (08876924), 2009, Vol 23, Issue 2, p313
- ISSN
0887-6924
- Publication type
Article
- DOI
10.1038/leu.2008.286