Drug response profiling can predict response to ponatinib in a patient with t(1;9)(q24;q34)-associated B-cell acute lymphoblastic leukemia

Abstract : Tyrosine kinase inhibitor (TKI)-based targeted therapy has significantly modified the outcome for patients with chronic myeloid leukemia (CML) in chronic phase. However, resistance remains a major concern in blastic phase of CML and in Philadelphia chromosome positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL). Second- and third-generation TKIs have been developed to overcome resistance to first generation drugs, but selecting the appropriate drug has become a challenge. Various tests are available to determine a patient’s disease status in CML including the mechanisms of resistance when involved, but clinical experience is limited in ALL, especially those with poorly defined ABL1 rearrangements. Here, we report a case of ALL associated with a t(1;9)(q24;q34) RCSD1-ABL1 rearrangement. We show how ex vivo drug response profiling (DRP) may help choose among various therapeutic options.