Nilotinib rapidly reverses breakpoint cluster region-Abelson oncogene fusion gene and M244V mutations in a patient with chronic myelogenous leukemia: A case report

Abstract

Chronic myelogenous leukemia (CML) is a condition characterized by a balanced genetic translocation, t (9;22) (q34;q11.2), which leads to a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is referred to as the Philadelphia chromosome. At a molecular level, this translocation results in the formation of the BCR-ABL fusion oncogene, which translates into a BCR-ABL oncoprotein. Imatinib, nilotinib and dasatinib are three tyrosine kinase inhibitors that have been approved by the US Food and Drug Administration for the treatment of patients diagnosed with CML in the chronic phase (CML-CP). The present study describes the case of a patient with imatinib-resistant CML who, following two months of treatment with nilotinib, no longer exhibited detectable BCR-ABL fusion genes or M244V mutations. This suggests that nilotinib may be effective for treating CML cases in which the BCR-ABL fusion protein has an M244V mutation.

Keywords: M244V mutation; breakpoint cluster region-Abelson oncogene; chronic myeloid leukemia; nilotinib; tyrosine kinase inhibitors.

Figure 1.

(A) ABL kinase region mutation, c.730 A>G (p.244V). (B) ALB kinase polymerase chain reaction analysis and sequencing found no mutations. ABL, Abelson oncogene.

Figure 2.

Correlation between the application of imatinib (IM), nilotinib (NT) and the BCR-ABL/ABL copy number ratio. BCR, breakpoint cluster region; ABL, Abelson oncogene; TKI, tyrosine kinase inhibitor.