Baassiri, A., Ghais, A., Kurdi, A., Rahal, E., Nasr, R., Shirinian, M. (2024). The molecular signature of BCR::ABL [P210] and BCR::ABL [T315I] in a Drosophila melanogaster chronic myeloid leukemia model.  iScience 27(4): 109538.

FBrf0259231

Research paper

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.

PMC10995885 (PMC) (EuropePMC)