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Current Hematologic Malignancy Reports

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01-04-2020 | Acute Lymphoblastic Leukemia | Acute Lymphocytic Leukemias (K Ballen and M Keng, Section Editors)

MLL-Rearranged Acute Lymphoblastic Leukemia

Authors: Firas El Chaer, Michael Keng, Karen K. Ballen

Published in: Current Hematologic Malignancy Reports | Issue 2/2020

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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Title: MLL-Rearranged Acute Lymphoblastic Leukemia
Authors: Firas El Chaer
Michael Keng
Karen K. Ballen
Publication date: 01-04-2020
Publisher: Springer US
Keywords: Acute Lymphoblastic Leukemia
Leukemia
Cytostatic Therapy
Published in: Current Hematologic Malignancy Reports / Issue 2/2020
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI: https://doi.org/10.1007/s11899-020-00582-5

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