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The FABD domain is critical for the oncogenicity of BCR/ABL in chronic myeloid leukaemia

dc.contributor.authorRenren Zheng
dc.contributor.authorWei Wei
dc.contributor.authorSuotian Liu
dc.contributor.authorDachuan Zeng
dc.contributor.authorZesong Yang
dc.contributor.authorJie Tang
dc.contributor.authorJinfeng Tan
dc.contributor.authorZhenglan Huang
dc.contributor.authorMiao Gao
dc.contributor.otherDepartment of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by Ministry of Education, School of Laboratory Medicine, Chongqing Medical University
dc.contributor.otherDepartment of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by Ministry of Education, School of Laboratory Medicine, Chongqing Medical University
dc.contributor.otherDepartment of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by Ministry of Education, School of Laboratory Medicine, Chongqing Medical University
dc.contributor.otherDepartment of Clinical Laboratory, Women and Children’s Hospital of Chongqing Medical University
dc.contributor.otherDepartment of Hematology, The First Affiliated Hospital of Chongqing Medical University
dc.contributor.otherDepartment of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by Ministry of Education, School of Laboratory Medicine, Chongqing Medical University
dc.contributor.otherDepartment of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by Ministry of Education, School of Laboratory Medicine, Chongqing Medical University
dc.contributor.otherDepartment of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated by Ministry of Education, School of Laboratory Medicine, Chongqing Medical University
dc.contributor.otherDepartment of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University
dc.date.accessioned2024-06-09T11:27:14Z
dc.date.accessioned2025-10-08T08:06:56Z
dc.date.available2025-10-08T08:06:56Z
dc.date.issued2024-06
dc.identifier.urihttp://digilib.fisipol.ugm.ac.id/repo/handle/15717717/35606
dc.description.abstractAbstract Background Abnormally expressed BCR/ABL protein serves as the basis for the development of chronic myeloid leukaemia (CML). The F-actin binding domain (FABD), which is a crucial region of the BCR/ABL fusion protein, is also located at the carboxyl end of the c-ABL protein and regulates the kinase activity of c-ABL. However, the precise function of this domain in BCR/ABL remains uncertain. Methods The FABD-deficient adenovirus vectors Ad-BCR/ABL△FABD, wild-type Ad-BCR/ABL and the control vector Adtrack were constructed, and 32D cells were infected with these adenoviruses separately. The effects of FABD deletion on the proliferation and apoptosis of 32D cells were evaluated by a CCK-8 assay, colony formation assay, flow cytometry and DAPI staining. The levels of phosphorylated BCR/ABL, p73, and their downstream signalling molecules were detected by western blot. The intracellular localization and interaction of BCR/ABL with the cytoskeleton-related protein F-actin were identified by immunofluorescence and co-IP. The effect of FABD deletion on BCR/ABL carcinogenesis in vivo was explored in CML-like mouse models. The degree of leukaemic cell infiltration was observed by Wright‒Giemsa staining and haematoxylin and eosin (HE) staining. Results We report that the loss of FABD weakened the proliferation-promoting ability of BCR/ABL, accompanied by the downregulation of BCR/ABL downstream signals. Moreover, the deletion of FABD resulted in a change in the localization of BCR/ABL from the cytoplasm to the nucleus, accompanied by an increase in cell apoptosis due to the upregulation of p73 and its downstream proapoptotic factors. Furthermore, we discovered that the absence of FABD alleviated leukaemic cell infiltration induced by BCR/ABL in mice. Conclusions These findings reveal that the deletion of FABD diminished the carcinogenic potential of BCR/ABL both in vitro and in vivo. This study provides further insight into the function of the FABD domain in BCR/ABL.
dc.language.isoEN
dc.publisherBMC
dc.subject.lccMedicine
dc.titleThe FABD domain is critical for the oncogenicity of BCR/ABL in chronic myeloid leukaemia
dc.typeArticle
dc.description.keywordsF-actin binding domain
dc.description.keywordsBCR/ABL
dc.description.keywordsChronic myeloid leukaemia
dc.description.keywordsOncogenicity
dc.description.keywordsp73
dc.description.pages1-13
dc.description.doi10.1186/s12964-024-01694-8
dc.title.journalCell Communication and Signaling
dc.identifier.e-issn1478-811X
dc.identifier.oai699d64ae3d1b4ce79f0523f833c618c7
dc.journal.infoVolume 22, Issue 1


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