Correlation of clinical response and response duration with miR-145 induction by lenalidomide in CD34+ cells from patients with del(5q) myelodysplastic syndrome.
|Authors||Venner CP, Wegrzyn Woltosz J, Nevill TJ, Deeg HJ, Caceres G, Platzbecker U, Scott BL, Sokol L, Sung S, List AF & Karsan A.|
|Abstract||We examined whether lenalidomide exposure upregulates miRNAs and mRNAs, previously shown to play a role in the disease phenotype of del(5q) myelodysplastic syndrome, in pretreatment CD34+ marrow cells. We hypothesized that increased expression would predict for clinical response. Changes in miR-143, miR-145, miR-146a, miR-146b, miR-378, miR-584, SPARC and RPS14 were examined in del(5q) (n = 10) and non-del(5q) (n = 18) myelodysplastic syndrome patient samples. Significantly increased expression of miR-143 (1.8-fold and 1.5-fold in del(5q) and non-del(5q), respectively), and miR-145 (1.9-fold and 1.6-fold in del(5q) and non-del(5q), respectively) was observed. In the del(5q) myelodysplastic syndrome cohort, transfusion independence correlated with a ≥1.3-fold increase in miR-145 expression and response >12 months correlated with ≥1.5-fold increase. Knockdown of miR-143 and miR-145 in cord blood CD34+ cells resulted in increased erythroid progenitor activity. Lenalidomide selectively abrogated progenitor activity in cells depleted of miR-143 and miR-145 supporting a key role for miR-143/145 in the sensitivity to lenalidomide of del(5q) myelodysplastic syndrome patients.|
|Journal Name and Citation||
Haematologica. 2012 Aug 28. [Epub ahead of print]
|Date of Publication||2012/08/28|