Tyrosine kinases in KMT2A/MLL-rearranged acute leukemias as potential therapeutic targets to overcome cancer drug resistance  

作　　者：Fatih M.Uckun Sanjive Qazi 

机构地区：[1]Ares Pharmaceuticals,St.Paul,MN 55110,USA

出　　处：《Cancer Drug Resistance》2022年第4期902-916,共15页癌症耐药（英文）

摘　　要：Aim:The main goal of this study was to elucidate at the transcript level the tyrosine kinase expression profiles of primary leukemia cells from mixed lineage leukemia 1 gene rearranged(KMT2A/MLL-R+)acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL)patients.Methods:We evaluated protein tyrosine kinase(PTK)gene expression profiles of primary leukemic cells in KMT2A/MLL-R+AML and ALL patients using publicly available archived datasets.Results:Our studies provided unprecedented evidence that the genetic signatures of KMT2A/MLL-R+AML and ALL cells are characterized by transcript-level overexpression of specific PTK.In infants,children and adults with KMT2A/MLL-R+ALL,as well as pediatric patients with KMT2A/MLL-R+AML,the gene expression levels for FLT3,BTK,SYK,JAK2/JAK3,as well as several SRC family PTK were differentially amplified.In adults with KMT2A/MLLR+AML,the gene expression levels for SYK,JAK family kinase TYK2,and the SRC family kinases FGR and HCK were differentially amplified.Conclusion:These results provide new insights regarding the clinical potential of small molecule inhibitors of these PTK,many of which are already FDA/EMA-approved for other indications,as components of innovative multimodality treatment platforms against KMT2A/MLL-R+acute leukemias.

关 键 词：AML ALL MLL gene tyrosine kinase LEUKEMIA 

分 类 号：R733.7[医药卫生—肿瘤]