BRCA1 Promoter Methylation Is Linked to Defective Homologous Recombination Repair and Elevated miR-155 to Disrupt Myeloid Differentiation in Myeloid Malignancies.

This study demonstrates frequent defective HR, associated with BRCA1 epigenetic silencing, in a broad range of myeloid neoplasms. The increased prevalence of BRCA1 promoter methylation, resulting in repressed BRCA1, may have an additional role in leukemogenesis by increasing miR-155 expression, which then inhibits transcription factors associated with normal myeloid differentiation. Further study of HR defects may facilitate the identification of HR-defective myeloid neoplasms sensitive to PARPi.