Tyrosine kinase inhibitor response of ABL-class acute lymphoblastic leukemia: the role of kinase type and SH3 domain

• DOI: 10.1182/blood.2023023120
• Publication Date: 2024-02-23T21:45:35Z
• Authors: Inge van Outersterp; Sarah K. Tasian; Caitlin E. J. Rei...; Aurélie Boeree; Hester A. de Groo...; Gabriele Escherich; Judith M. Boer; Monique L. den Boer
• Keywords: ABL; PDGFRB; Imatinib Mesylate; Bosutinib

Acute lymphoblastic leukemia (ALL) with fusions of ABL-class tyrosine kinase genes other than BCR::ABL1 occurs in ∼3% children ALL. The involved this BCR::ABL1-like (Ph-like) subtype include ABL1, PDGFRB, ABL2, and CSF1R, each which has up to 10 described partner genes. ALL resembles BCR::ABL1-positive a similar gene expression profile, poor response chemotherapy, sensitivity inhibitors (TKIs). There is lack comprehensive data regarding TKI the heterogeneous group We observed variability within among subgroup. showed that samples for any 4 were relatively sensitive imatinib. In contrast, PDGFRB-fused less dasatinib bosutinib. Variation ex vivo subset same was not associated immunophenotype, 5' fusion partner, presence or absence Src-homology-2/3 domains, deletions IKZF1, PAX5, CDKN2A/B. conclusion, main determinant relevant specific selection.