MLL-Rearranged Acute Lymphoblastic Leukemia

被引:70
作者
El Chaer, Firas [1 ]
Keng, Michael [1 ]
Ballen, Karen K. [1 ]
机构
[1] Univ Virginia, Sch Med, Dept Med, Div Hematol & Oncol, 1215 Lee St, Charlottesville, VA 22903 USA
关键词
Acute lymphoblastic leukemia; MLL; KMT2A; Resistance; STEM-CELL TRANSPLANTATION; POOR PROGNOSTIC SUBGROUP; GENE-EXPRESSION; TRANSCRIPTIONAL ELONGATION; DROSOPHILA-TRITHORAX; CYTOSINE-ARABINOSIDE; ANTIGEN-EXPRESSION; RAS MUTATIONS; IN-VITRO; FUSION;
D O I
10.1007/s11899-020-00582-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:83 / 89
页数:7
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