The molecular signature of BCR::ABLP210 and BCR::ABLT315I in a Drosophila melanogaster chronic myeloid leukemia model
Amro Baassiri,
Ali Ghais,
Abdallah Kurdi,
Elias Rahal,
Rihab Nasr,
Margret Shirinian
Affiliations
Amro Baassiri
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
Ali Ghais
Department of Experimental Pathology and Immunology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
Abdallah Kurdi
Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
Elias Rahal
Department of Experimental Pathology and Immunology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Center for Infectious Diseases Research, American University of Beirut Medical Center, Beirut, Lebanon
Rihab Nasr
Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Corresponding author
Margret Shirinian
Department of Experimental Pathology and Immunology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Center for Infectious Diseases Research, American University of Beirut Medical Center, Beirut, Lebanon; Corresponding author
Summary: Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder resulting from a balanced translocation leading to BCR::ABL1 oncogene with increased tyrosine kinase activity. Despite the advancements in the development of tyrosine kinase inhibitors (TKIs), the T315I gatekeeper point mutation in the BCR::ABL1 gene remains a challenge. We have previously reported in a Drosophila CML model an increased hemocyte count and disruption in sessile hemocyte patterns upon expression of BCR::ABL1p210 and BCR::ABL1T315I in the hemolymph. In this study, we performed RNA sequencing to determine if there is a distinct gene expression that distinguishes BCR::ABL1p210 and BCR::ABL1T315I. We identified six genes that were consistently upregulated in the fly CML model and validated in adult and pediatric CML patients and in a mouse cell line expressing BCR::ABL1T315I. This study provides a comprehensive analysis of gene signatures in BCR::ABL1p210 and BCR::ABL1T315I, laying the groundwork for targeted investigations into the role of these genes in CML pathogenesis.
