MLL-Rearranged Acute Lymphoblastic Leukemia

Curr Hematol Malig Rep. 2020 Apr;15(2):83-89. doi: 10.1007/s11899-020-00582-5.


Purpose of review: Rearrangements of the histone lysine [K]-MethylTransferase 2A gene (KMT2A) gene on chromosome 11q23, formerly known as the mixed-lineage leukemia (MLL) gene, are found in 10% and 5% of adult and children ALL cases, respectively. The most common translocated genes are AFF1 (formerly AF4), MLLT3 (formerly AF9), and MLLT1 (formerly ENL). The bimodal incidence of MLL-r-ALL usually peaks in infants in their first 2 years of life and then declines thereafter during the pediatric/young adult phase until it increases again with age. MLL-rearranged ALL (MLL-r-ALL) is characterized by hyperleukocytosis, aggressive behavior with early relapse, relatively high incidence of central nervous system (CNS) involvement, and poor prognosis.

Recent findings: MLL-r-ALL cells are characterized by relative resistance to corticosteroids (due to Src kinase-induced phosphorylation of annexin A2) and L-asparaginase therapy, but they are sensitive to cytarabine chemotherapy (due to increased levels of hENT1 expression). Potential therapeutic targets include FLT3 inhibitors, MEK inhibitors, HDAC inhibitors, BCL-2 inhibitors, MCL-1 inhibitors, proteasome inhibitors, hypomethylating agents, Dot1L inhibitors, and CDK inhibitors. In this review, we discuss MLL-r-ALL focusing on clinical presentation, risk stratification, drug resistance, and treatment strategies, including potential novel therapeutic targets.

Keywords: Acute lymphoblastic leukemia; KMT2A; MLL; Resistance.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Drug Resistance, Neoplasm / genetics
  • Gene Rearrangement*
  • Genetic Predisposition to Disease
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Molecular Targeted Therapy
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Phenotype
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Risk Factors
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase