Ngankeu, ApollinaireRanganathan, ParvathiHavelange, ViolaineNicolet, DeedraVolinia, StefanoPowell, Bayard L.Kolitz, Jonathan E.Uy, Geoffrey L.Stone, RichardKornblau, Steven M.Andreeff, MichaelCroce, Carlo M.Bloomfield, Clara D.Garzon, Ramiro2018-03-202018Ngankeu, A., P. Ranganathan, V. Havelange, D. Nicolet, S. Volinia, B. L. Powell, J. E. Kolitz, et al. 2018. “Discovery and functional implications of a miR-29b-1/miR-29a cluster polymorphism in acute myeloid leukemia.” Oncotarget 9 (4): 4354-4365. doi:10.18632/oncotarget.23150. http://dx.doi.org/10.18632/oncotarget.23150.http://nrs.harvard.edu/urn-3:HUL.InstRepos:35014953We previously reported that microRNA (miR)-29b is down-regulated and has a tumor suppressor role in acute myeloid leukemia (AML). However, little is known about the mechanisms responsible for miR-29b expression downregulation in AML. In this work we screened for mutations that could affect miR-29b expression. Using Sanger sequencing, we identified a germline thymidine (T) base deletion within the miR-29b-1/miR-29a cluster precursor in 16% of AML patients. Remarkably we found a significant enrichment for the presence of the miR-29 polymorphism in core binding factor (CBF) newly diagnosed AML patients (n = 61/303; 20%) with respect to age, sex and race matched controls (n = 43/402:11%, P < 0.01). Mechanistically, this polymorphism affects the expression ratio of mature miR-29b and miR-29a by dampening the processing of miR-29a. RNA immunoprecipitation assays showed reduced DROSHA binding capacity to the polymorphism with respect to the controls. Finally, we showed that this polymorphism negatively impacts the ability of miR-29b-1/miR-29a cluster to target MCL-1 and CDK6, both known miR-29 targets.en-USpolymorphismmiR-29b-1/miR-29a clusterAMLJournal Article2018-03-2010.18632/oncotarget.23150