PDGFRB mutation and tyrosine kinase inhibitor resistance in Ph-like acute lymphoblastic leukemia

In this study, we identified a novel PDGFRB fusion gene, namely AGGF1-PDGFRB, and functionally characterized its oncogenic potential in vitro. Further genomic profiling of longitudinally collected samples during treatment revealed the emergence of a mutation, PDGFRBC843G, which directly conferred resistance to all generations of ABL TKIs, including imatinib, dasatinib, nilotinib, and ponatinib. PDGFRB-mutant leukemia cells are highly sensitive to multitarget kinase inhibitor CHZ868, suggesting potential therapeutic options for some patients resistant to ABL TKIs. In summary, we describe a complex clonal evolution pattern in Ph-like ALL and identified a novel PDGFRB point mutation that drives leukemia relapse after ABL TKI treatment.

Source: Blood - May 17, 2018 Category: Hematology Authors: Zhang, Y., Gao, Y., Zhang, H., Zhang, J., He, F., Hnizda, A., Qian, M., Liu, X., Gocho, Y., Pui, C.-H., Cheng, T., Wang, Q., Yang, J. J., Zhu, X., Liu, X. Tags: Free Research Articles, Lymphoid Neoplasia, CME article, Brief Reports Source Type: research