Most chronic myeloid leukaemia (CML) patients are genetically characterized by the t(9;22)(q34;q11), generating the BCR/ABL1 fusion gene. However, a few CML patients with rearrangements of 9q34 and 12p13, leading to ETV6/ABL1 chimaeras, have also been reported. Here we describe the clinical and genetic response to imatinib mesylate treatment of an ETV6/ABL1-positive CML patient diagnosed in blast crisis (BC). A chronic phase was achieved after acute myeloid leukaemia induction therapy. Then, treatment with imatinib mesylate (600 mg/d) was initiated and the effect was assessed clinically as well as genetically, including by repeated interphase fluorescence in situ hybridization studies. Until d 71 of imatinib mesylate therapy, stable improvements in the clinical and laboratory features were noted, and the frequency of ABL1-rearranged peripheral blood cells decreased from 56% to 11%. At d 92, an additional t(12;13)(p12;q13), with the 12p breakpoint proximal to ETV6, was found. The patient relapsed into BC 126 d after the start of the imatinib mesylate treatment and succumbed to the disease shortly afterwards. No mutations in the tyrosine kinase domain of ABL1 of the ETV6/ABL1 fusion were identified in the second BC. However, whereas the ETV6/ABL1 expression was seemingly the same at diagnosis and at second BC, the expression of ETV6 was markedly lower at the second BC. This decreased expression of wild-type ETV6 may have been a contributory factor for the relapse
