Restoration of donor chimerism by nilotinib in a chronic myeloid leukaemia patient post mutation-associated imatinib mesylate resistance and allogeneic stem cell transplant failure

Abstract

Chronic myeloid leukaemia is a haematopoietic stem cell malignancy characterized by the p210 BCR-ABL1/ABL1 oncoprotein. Treatment for CML and a subset of ALL patients has been revolutionized by the advent of imatinib mesylate,1 a tyrosine kinase inhibitor, which replaced IFN-α and haematopoietic stem cell transplant (SCT) as front-line therapy.2 DNA mutations in the BCR-ABL1 kinase domain, to which imatinib mesylate binds, may result in the loss of imatinib mesylate binding and drug resistance.3 Second-generation TKIs, dasatinib and nilotinib, retain binding in the presence of the majority of BCR-ABL1 kinase domain mutations because of improved topological fit to the enzyme4, 5and show promise in the treatment of patients with resistant disease.6, 7