Case Report

International Journal of Hematology

, Volume 93, Issue 2, pp 243-246

First online:

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

  • Masaya OkadaAffiliated withDivision of Hematology, Department of Internal Medicine, Hyogo College of Medicine
  • , Atsushi SatakeAffiliated withDivision of Hematology, Department of Internal Medicine, Hyogo College of Medicine
  • , Katsuji KaidaAffiliated withDivision of Hematology, Department of Internal Medicine, Hyogo College of Medicine
  • , Kyoko TaniguchiAffiliated withDivision of Hematology, Department of Internal Medicine, Hyogo College of Medicine
  • , Satoshi YoshiharaAffiliated withDivision of Hematology, Department of Internal Medicine, Hyogo College of Medicine
  • , Kazuhiro IkegameAffiliated withDivision of Hematology, Department of Internal Medicine, Hyogo College of Medicine
  • , Hiroya TamakiAffiliated withDivision of Hematology, Department of Internal Medicine, Hyogo College of MedicineLaboratory of Cell Transplantation, Institute for Advanced Medical Sciences, Hyogo College of Medicine
  • , Toshihiro SomaAffiliated withDivision of Hematology, Department of Internal Medicine, Hyogo College of Medicine
  • , Yoshihiro FujimoriAffiliated withLaboratory of Cell Transplantation, Institute for Advanced Medical Sciences, Hyogo College of Medicine Email author 
    • , Hiroyasu OgawaAffiliated withDivision of Hematology, Department of Internal Medicine, Hyogo College of MedicineLaboratory of Cell Transplantation, Institute for Advanced Medical Sciences, Hyogo College of Medicine

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

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.

Keywords

Chronic myelogenous leukemia Variant Philadelphia chromosome Point mutation Nilotinib