In-silico probing of AML related RUNX1 cancer-associated missense mutations: Predicted relationships to DNA binding and drug interactions.

ABSTRACT: The molecular consequences of cancer associated mutations in Acute myeloid leukemia (AML) linked factors are not very well understood. Here, we interrogated the COSMIC database for missense mutations associated with the RUNX1 protein, that is frequently mis-regulated in AML, where we sought to identify recurrently mutated positions at the DNA-interacting interface. Indeed, six of the mutated residues, out of a total 417 residues examined within the DNA binding domain, evidenced reduced DNA association in in silico predictions. Further, given the prominence of RUNX1's compromised function in AML, we asked the question if the mutations themselves might alter RUNX1's interaction (off-target) with known FDA-approved drug molecules, including three currently used in treating AML. We iden

SUBMITTER: Ullah H 

PROVIDER: S-EPMC9454315 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature