New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?

Abstract

In chronic myeloid leukemia (CML) the presence of mutations in the tyrosine kinase domain (TK) of the normalABL1 gene is the most common cause of loss of response to treatment. Detection of these mutations is an important study because it allows the choice of most suitable TK inhibitor. We report a new mutation L324M that has not been detected so far. It is a case of a 44 year old male with CML chronic phase diagnosis in February 1996, who was treated from 2001 to 2006 with Imatinib. From February 2006 to May 2011 he was treated with decreasing doses of Dasatinib due to intolerance to the drug. At that time the patient showed loss of cytogenetic response and the presence of the mutation L324M by direct sequencing. Because of these finding, treatment was changed to 600 mg/day Nilotinib. After three months of treatment the mutation becomes undetectable and major molecular response (BCR-ABL1<0.1%) was achieved at 12 months. Our data suggest that the L324M mutation is sensitive to Nilotinib treatment.