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 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::ABL1^p210 and BCR::ABL1^T315I in the hemolymph. In this study, we performed RNA sequencing to determine if there is a distinct gene expression that distinguishes BCR::ABL1^p210 and BCR::ABL1^T315I. 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::ABL1^T315I. This study provides a comprehensive analysis of gene signatures in BCR::ABL1^p210 and BCR::ABL1^T315I, laying the groundwork for targeted investigations into the role of these genes in CML pathogenesis.