Successful treatment with nilotinib after imatinib failure in a CML patient with a four-way Ph chromosome translocation and point mutations in BCR/ABL gene
- First Online:
- 156 Downloads
Chronic myelogenous leukemia (CML) is characterized by Philadelphia (Ph) chromosome with a chimeric gene BCR–ABL created by reciprocal t(9:22) (q34;q11) translocation. Variant Ph chromosome translocations involving chromosomes other than 9 and 22 are found in 5–10% of CML cases. We here report a CML patient who carries a four-way Ph chromosome translocation, t(9;22;15;19) (q34;q11;q15;q13). The patient was diagnosed in 1997 and initially treated with hydroxyurea. In 2002, treatment with imatinib, a selective BCR–ABL tyrosine kinase inhibitor (TKI), was started but Ph-positive chromosomes remained at the levels of 42–65%, indicating imatinib failure. In 2006, the point mutations of F359I and L387M were detected in BCR/ABL gene, which may be related to imatinib failure. Treatment with nilotinib, a TKI with high target specificity, was then started which resulted in durable major molecular response. Administration of nilotinib offered an effective treatment in a CML patient with variant Ph chromosome translocations and BCR–ABL point mutations after imatinib failure.
KeywordsChronic myelogenous leukemia Variant Philadelphia chromosome Point mutation Nilotinib
- 7.Silver RT, Talpaz M, Sawyers CL, Druker BJ, Hochhaus A, Schiffer CA, et al. Four years of follow-up of 1027 patients with late chronic phase (L-CP), accelerated phase (AP), or blast crisis (BC) chronic myeloid leukemia (CML) treated with imatinib in three large phase II trials. Blood. 2004;104:11a (abstract).Google Scholar
- 10.Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, et al. Nilotinib (formerly AMN107), a highly selective BCR–ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2007;110:3540–6.CrossRefPubMedGoogle Scholar
- 11.le Coutre P, Ottmann OG, Giles F, Kim DW, Cortes J, Gattermann N, et al. Nilotinib (formerly AMN107), a highly selective BCR–ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia. Blood. 2008;111:1834–9.CrossRefPubMedGoogle Scholar
- 17.Mitelman F, Johansson B, Mertens F. Mitelman database of chromosome aberrations in cancer. 2010. http://cgap.nci.nih.gov/Chromosomes/Mitelman.
- 27.Jakubowska J, Czyz M. Novel inhibitors of BCR–Abl. Postepy Hig Med Dosw. 2006;60:697–706 (Polish, online).Google Scholar