Targeting CDK6 and BCL2 Exploits the "MYB Addiction" of Ph⁺ Acute Lymphoblastic Leukemia.

ABSTRACT: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph⁺ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1-dependent and -independent mechanisms. Newly developed TKI can target Ph⁺ ALL cells with BCR-ABL1-dependent resistance; however, overcoming BCR-ABL1-independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Ph⁺ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced Ph⁺ ALL

SUBMITTER: De Dominici M 

PROVIDER: S-EPMC5815914 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature