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MLL-Rearranged Acute Lymphoblastic Leukemia

  • Acute Lymphocytic Leukemias (K Ballen and M Keng, Section Editors)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

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.

Summary

In this review, we discuss MLL-r-ALL focusing on clinical presentation, risk stratification, drug resistance, and treatment strategies, including potential novel therapeutic targets.

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  1. Department of Medicine, Division of Hematology and Oncology, University of Virginia School of Medicine, 1215 Lee Street, Charlottesville, VA, 22903, USA

    Firas El Chaer, Michael Keng & Karen K. Ballen

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  1. Firas El Chaer
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El Chaer, F., Keng, M. & Ballen, K.K. MLL-Rearranged Acute Lymphoblastic Leukemia. Curr Hematol Malig Rep 15, 83–89 (2020). https://doi.org/10.1007/s11899-020-00582-5

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