The role of RAS mutations in MLL-rearranged leukaemia: A path to intervention?

Biochim Biophys Acta Rev Cancer. 2017 Dec;1868(2):521-526. doi: 10.1016/j.bbcan.2017.10.005. Epub 2017 Oct 19.

Abstract

Childhood acute lymphoblastic leukaemia (ALL) with MLL rearrangement (MLL-r) is an aggressive disease still associated with a high mortality rate. Recent investigations have identified co-operating mutations in the RAS pathway and although the functional consequences of these mutations are not yet fully understood, aberrant regulation of RAS pathway signalling at both transcriptional and protein levels is observed. Studies investigating the efficacy of specific inhibitors of this pathway, e.g. MEK-inhibitors, have also achieved encouraging results. In this context, this mini-review summarizes the available data surrounding MLL-r infant ALL with RAS mutation in relation to other well-known features of this intriguing disease.

Keywords: Acute lymphoblastic leukaemia; MLL; Prognosis; RAS; Targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Gene Rearrangement*
  • Genes, ras*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mutation*
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / etiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors

Substances

  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3
  • Mitogen-Activated Protein Kinase Kinases