c-myb is involved in CML progression and is a therapeutic target in the zebrafish CML model  

作　　者：Yin Ye Xiaojun Yang Feifei Li Wei Liu Wenqing Zhang Zhibin Huang 

机构地区：[1]Division of Cell,Developmental and Integrative Biology,School of Medicine,South China University of Technology,Guangzhou,China

出　　处：《Animal Models and Experimental Medicine》2024年第2期136-144,共9页动物模型与实验医学（英文）

基　　金：National Key R&D Program of China;Grant/Award Number:2018YFA0801000;National Natural Science Foundation of China;Grant/Award Number:32170830;Natural Science Foundation of Guangdong Province;China;Grant/Award Number:2021A1515010422;South China University of Technology。

摘　　要：Background:Despite the success of tyrosine kinase inhibitors in chronic myeloid leukemia(CML)therapy,CML still faces the challenges of drug resistance and progression to blast crisis.Twenty-five percent of patients have imatinib resistance and treatment difficulties due to heterogeneity after progression,but little is known about the mechanism.A key transcription factor in hematopoiesis,MYB,has been reported to increase abnormally in several types of aggressive blood disorders including CML.Methods:This study used a zebrafish model to explore the relationship between BCR/ABL1 and c-myb in CML progression.A CML zebrafish model was crossed with a c-myb hyperactivity transgenic line.Results:It was found that both exogenous BCR/ABL1 and c-myb could up-regulate the expression of neutrophil-related genes.More seriously,neutrophil accumulation was observed when BCR/ABL1 was combined with c-myb overexpression.Further studies showed that c-myb may be one of the downstream targets of BCR/ABL1 and the effect of BCR/ABL1 on neutrophils was c-myb dependent.Taking advantage of this inheritable in vivo model,it was shown that a combination of imatinib and flavopiridol,a cyclin-dependent kinase inhibitor targeting MYB,could more effectively alleviate the aggressive phenotype of the double transgene line.Conclusion:In summary,this study suggests that c-myb acts downstream of BCR/ABL1 and is involved in CML progression and is therefore a risk factor and a valuable target for the treatment of CML progression.The model used in the study could be helpful in high-throughput drug screening in CML transformation.

关 键 词：chronic myeloid leukemia C-MYB FLAVOPIRIDOL zebrafish model 

分 类 号：R733.72[医药卫生—肿瘤] R-332[医药卫生—临床医学]