The clinical outcomes of chronic myeloid leukemia patients harboring alternatively spliced BCR-ABL variants

ABSTRACTObjectives and importance: Tyrosine kinase inhibitors (TKIs) are indispensable for the treatment of chronic myeloid leukemia (CML). However, alternative splicing variants have been recently proposed as mechanisms of TKI resistance, although the clinical significance of these mutations remains controversial. We here present the long-term clinical courses of three CML patients harboring such unique mutations and try to assess their clinical significances. Moreover, the exon 6 frameshift presented here has been rarely reported, which may provide important information on this rare mutation.Clinical presentation: We report three cases of CML harboring an exon 7 deletion, insertion of 35 intronic nucleotides and an exon 6 frameshift, respectively. Remarkably, all patients obtained better than molecular response4.0 following administration of TKIs.Discussion and conclusion: Three CML cases highlighted an association between such splicing variants and clinical outcomes. The premature termination in the ki...