| First Author | Asslaber D | Year | 2010 |
| Journal | Blood | Volume | 115 |
| Issue | 21 | Pages | 4191-7 |
| PubMed ID | 20089965 | Mgi Jnum | J:160270 |
| Mgi Id | MGI:4453948 | Doi | 10.1182/blood-2009-07-234823 |
| Citation | Asslaber D, et al. (2010) microRNA-34a expression correlates with MDM2 SNP309 polymorphism and treatment-free survival in chronic lymphocytic leukemia. Blood 115(21):4191-7 |
| abstractText | In chronic lymphocytic leukemia (B-CLL), aberrations along the p53 axis lead to decreased overall survival and therapy resistance. Recent studies identified microRNA-34a (miR-34a) as a major downstream target of p53. We monitored the expression of miR-34a during disease development in a murine B-CLL model. miR-34a was up-regulated more than 20-fold during the leukemic but not during the preleukemic phase. In the human system, B-CLL cells also had 4.6-fold higher miR-34a expression compared with B cells of healthy controls. In B-CLL cells of patients with p53 aberrations, miR-34a expression was consistently low. The broad distribution of miR-34a levels in p53 wild-type patients prompted us to study the correlation between single nucleotide polymorphism 309 (SNP309) in the intronic promoter of MDM2 and miR-34a expression. B-CLL cells of patients with the SNP309 GG genotype had significantly lower miR-34a expression levels compared with patients with the TT genotype (P = .002). Low miR-34a levels were able to predict shorter time to treatment (P = .003) and were associated with an abbreviated lymphocyte doubling time. Further, overexpression of miR-34a in primary B-CLL cells induced apoptosis. These findings suggest miR-34a as a possible therapeutic avenue and a sensitive indicator of the activity of the p53 axis in B-CLL. |
