MLL -Rearranged Acute Lymphoblastic Leukemia

AbstractPurpose of ReviewRearrangements of the histonelysine [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 areAFF1 (formerlyAF4),MLLT3 (formerlyAF9), andMLLT1 (formerlyENL). The bimodal incidence ofMLL-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 FindingsMLL-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 ofhENT1 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.SummaryIn this review, we discussMLL-r-ALL focusing on clinical presentation, risk stratification, drug resistance, and treatment strategies, including potential novel therapeutic targets.
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research