Letter to the Editor Diagnostic Hematology Rapid Sequential Gain of ABL1 Kinase Domain Mutations with a Complex Karyotype in the Progression of Chronic Myelogenous Leukemia

CML is a myeloproliferative disease characterized by the Phila-delphia (Ph) chromosome, in which the oncogenic BCR-ABL1 fusion gene encodes a constitutively active tyrosine kinase. First-line treatment using the BCR-ABL tyrosine kinase inhibitor (TKI) imatinib has significantly changed the disease course of CML [1]. However, some patients develop resistance to this agent, largely due to point mutations within the ABL1 kinase domain (KD) [2, 3]. Resistance to imatinib may be overcome by treatment with second-line TKIs, including dasatinib, nilotinib, and bosutinib, which are active against most mutations; however, some muta-tions bring about resistance to these second-line drugs as well [4-6]. Therefore, a mutation analysis is recommended when choosing a second-line TKI [7]. We describe a CML patient who rapidly progressed to blast crisis following the sequential acquisi-tion of ABL1 KD mutations with a complex karyotype