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 Yin Ye;Xiaojun Yang;Feifei Li;Wei Liu;Wenqing Zhang;Zhibin Huang

作者机构：Division of CellDevelopmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhouChina 

出 版 物：《Animal Models and Experimental Medicine》 (动物模型与实验医学（英文）)

年 卷 期：2024年第7卷第2期

页      面：136-144页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

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 

主　　题：chronic myeloid leukemia c-myb flavopiridol zebrafish model 

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 ***-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 ***: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 ***:It was found that both exogenous BCR/ABL1 and c-myb could up-regulate the expression of neutrophil-related *** seriously,neutrophil accumulation was observed when BCR/ABL1 was combined with c-myb *** 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 *** 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 ***: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 *** model used in the study could be helpful in high-throughput drug screening in CML transformation.