Functional diversity of inhibitors tackling the differentiation blockage of MLL-rearranged leukemia.

ABSTRACT:

Introduction

The chromosomal rearrangements of the mixed-lineage leukemia gene MLL (KMT2A) have been extensively characterized as a potent oncogenic driver in leukemia. For its oncogenic function, most MLL-fusion proteins exploit the multienzyme super elongation complex leading to elevated expression of MLL target genes. High expression of MLL target genes overwrites the normal hematopoietic differentiation program, resulting in undifferentiated blasts characterized by the capacity to self-renew. Although extensive resources devoted to increased understanding of therapeutic targets to overcome de-differentiation in ALL/AML, the inter-dependencies of targets are still not well described. The majority of inhibitors potentially interfering with MLL-fusion protein driven transformation

SUBMITTER: Brzezinka K 

PROVIDER: S-EPMC6599250 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature