Abivertinib,a third-generation tyrosine kinase inhibitor,is originally designed to target epidermal growth factor receptor(EGFR)-activating mutations.Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer.However,abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3.Given that these kinases play some roles in the progression of megakaryopoiesis,we speculate that abivertinib can affect megakaryocyte(MK)differentiation and platelet biogenesis.We treated cord blood CD34+hematopoietic stem cells,Meg-01 cells,and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis.Our in vitro results showed that abivertinib impaired the CFU-MK formation,proliferation of CD34+HSC-derived MK progenitor cells,and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation.These results suggested that megakaryopoiesis was inhibited by abivertinib.We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice,which suggested that thrombopoiesis was also inhibited.Thus,these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.

Jiansong Huang;Xin Huang;Yang Li;Xia Li;Jinghan Wang;Fenglin Li;Xiao Yan;Huanping Wang;Yungui Wang;Xiangjie Lin;Jifang Tu;Daqiang He;Wenle Ye;Min Yang;Jie Jin

Department of Hematology,Key Laboratory of Hematologic Malignancies,Diagnosis and Treatment,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Institute of Hematology,Zhejiang University School of Medicine,Hangzhou 310003,China;Department of Obstetrics,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Department of Hematology,Qingdao Municipal Hospital,Qingdao 266000,China;Department of Laboratory Medicine,Affiliated Hangzhou First People's Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Cancer Center Zhejiang University,Hangzhou 310058,China

医学前沿

[1]Jiansong Huang;Xin Huang;Yang Li;Xia Li;Jinghan Wang;Fenglin Li;Xiao Yan;Huanping Wang;Yungui Wang;Xiangjie Lin;Jifang Tu;Daqiang He;Wenle Ye;Min Yang;Jie Jin-.Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis)[J].医学前沿,2022(03):416-428

Abivertinib,megakaryocyte,abivertinib,megakaryopoiesis,CD34+hematopoietic,CD34+HSC,MKs,thrombopoiesis,thrombocythemia

inhibits,differentiation,platelet,biogenesis,third,generation,tyrosine,originally,designed,target,epidermal,growth,receptor,EGFR,activating,mutations,Previous,studies,have,shown,that,has,promising,antitumor,activity,well,tolerated,safety,profile,patients,small,lung,cancer,However,also,exhibited,high,inhibitory,against,Bruton,Janus,Given,these,kinases,play,some,roles,progression,speculate,affect,We,treated,cord,blood,stem,cells,Meg,C57BL,mice,observed,determine,biological,effect,Our,vitro,results,showed,impaired,CFU,formation,proliferation,derived,progenitor,functions,inhibited,These,suggested,was,by,demonstrated,vivo,decreased,number,bone,marrow,counts,which,Thus,preclinical,data,collectively,could,might,agent

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