MLL-rearranged infant leukaemia: A 'thorn in the side' of a remarkable success story

Biochim Biophys Acta Gene Regul Mech. 2020 Aug;1863(8):194564. doi: 10.1016/j.bbagrm.2020.194564. Epub 2020 May 3.

Abstract

Advances in treatment of childhood leukaemia has led to vastly improved survival rates, however some subtypes such as those characterised by MLL gene rearrangement (MLL-r), especially in infants, continue to have high relapse rates and poor survival. Natural history and molecular studies indicate that infant acute lymphoblastic leukaemia (ALL) originates in utero, is distinct from childhood ALL, and most cases are caused by MLL-r resulting in an oncogenic MLL fusion protein. Unlike childhood ALL, only a very small number of additional mutations are present in infant ALL, indicating that MLL-r alone may be sufficient to give rise to this rapid onset, aggressive leukaemia in an appropriate fetal cell context. Despite modifications in treatment approaches, the outcome of MLL-r infant ALL has remained dismal and a clear understanding of the underlying biology of the disease is required in order to develop appropriate disease models and more effective therapeutic strategies.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Tumor
  • DNA Methylation
  • Gene Rearrangement
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Infant
  • Infant, Newborn
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Myeloid-Lymphoid Leukemia Protein / metabolism*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology

Substances

  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase