MLL

Abstract

The human myeloid/lymphoid leukemia or mixed lineage leukemia (MLL) gene encodes a large nuclear protein that assembles in a high-molecular-weight complex. This MLL complex modifies the chromatin at distinct residues, thereby marking selected chromatin areas of our chromosomes for active transcription. The MLL complex makes part of a process designated as ‘cellular programming’, and counteracts Polycomb repressor complexes that disable large parts of our chromosomes for active transcription. The MLL complex plays a crucial role during embryonic development and maintains the tissue identity in the adult organism. Unfortunately, the MLL gene exhibits an intrinsic genetic instability that results in illegitimate recombination events involving more than 70 MLL translocation partners that have been so far characterized at the molecular level. In all these somatic recombination events, the MLL gene becomes disrupted in the breakpoint cluster region, dividing the MLL gene into an N- and a C-terminal gene portion which are fused to gene segments of a recombination partner. This leads to the expression of MLL fusion proteins that are correlated with leukemia development, either acute myeloid leukemia or acute lymphoblastic leukemia. MLL-rearranged leukemia is a hard-to-treat disease and the overall survival of these patients is still poor. About 5–10% of all acute leukemia patients carry such MLL-rearrangements. Recent scientific discoveries have shed light onto the cancer mechanisms behind certain MLL fusions, which gives hope that future developments may hold the promise for targeted therapy in these cancer patients.