The molecular signature of BCR::ABL P210 and BCR::ABL T315I in a Drosophila melanogaster chronic myeloid leukemia model

Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder resulting from a balanced translocation leading to 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 CML model an increased hemocyte count and disruption in sessile hemocyte patterns upon expression of and in the hemolymph. In this study, we performed RNA sequencing to determine if there is a distinct gene expression that distinguishes and . 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 . This study provides a comprehensive analysis of gene signatures in and , laying the groundwork for targeted investigations into the role of these genes in CML pathogenesis.