Mechanisms of mixed-lineage leukemia

Advances in our understanding of the genetic determinants of leukemia have translated to better treatment options and improved survival of patients with acute myeloid and acute lymphoid leukemia. However, some leukemias, such as those bearing 11q23 (MLL) translocations, result in aggressive diseases with a relatively poor prognosis, despite improved treatments such as allogeneic hematopoietic stem cell transplantation. This article will briefly review the functions and regulation of wild-type MLL during normal hematopoiesis, while focusing on recent advances in our understanding of the molecular mechanisms governing MLL leukemias. The transcriptional targets, cooperating signaling pathways and molecular machinery involved in MLL-associated leukemias will be discussed, as well as how these may be harnessed for more personalized treatment of this disease.