Emerging molecular subtypes and therapeutic targets in B-cell precursor acute lymphoblastic leukemia

• 作者: Jianfeng Li Yuting Dai Liang Wu Ming Zhang Wen Ouyang Jinyan Huang Saijuan Chen
• 来源期刊: 医学前沿
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: Reviews
• 页码范围: 347-371
• 页数: 25页
• 语种: 英文

摘要

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by genetic alterations with high heterogeneity.Precise subtypes with distinct genomic and/or gene expression patterns have been recently revealed using high-throughput sequencing technology.Most of these profiles are associated with recurrent non-overlapping rearrangements or hotspot point mutations that are analogous to the established subtypes,such as DUX4 rearrangements,MEF2D rearrangements,ZNF384/ZNF362 rearrangements,NUTM1 rearrangements,BCL2/MYC and/or B CL6 rearrangements,ETV6-RUNX1-llke gene expression,PAX5alt (diverse PAX5 alterations,including rearrangements,intragenic amplifications,or mutations),and hotspot mutations PAX5 (p.Pro80Arg)with biallellc PAX5 alterations,IKZF1 (p.Asn159Tyr),and ZEB2 (p.His1038Arg).These molecular subtypes could be classified by gene expression patterns with RNA-seq technology.Refined molecular classification greatly improved the treatment strategy.Multiagent therapy regimens,including target inhibitors (e.g.,imatinib),immunomodulators,monoclonal antibodies,and chimeric antigen receptor T-cell (CAR-T) therapy,are transforming the clinical practice from chemotherapy drugs to personalized medicine in the field of risk-directed disease management.We provide an update on our knowledge of emerging molecular subtypes and therapeutic targets in BCP-ALL.