title: Clonal chromosomal abnormalities in Philadelphia-negative cells in chronic myeloid leukemia patients treated with nilotinib used in first-line therapy.
abstract: Nilotinib is an effective option for the first-line treatment of chronic myeloid leukemia (CML) patients in chronic phase (CP). In CML patients, clonal cytogenetic abnormalities (CAs) in Philadelphia-negative (Ph-) metaphases have been widely observed after treatment with imatinib, or dasatinib/nilotinib following failure with imatinib. However, such abnormalities in CML patients treated with nilotinib as the first-line therapy have not been reported. Thirteen CML CP patients with Philadelphia-positive (Ph+) cells were initially diagnosed in our hospital from December 2010 to July 2011. Patients were followed up by clinical assessment, cytogenetic analysis, and BCR-ABL transcriptional level every 3 to 6 months. Retrospective fluorescence in situ hybridization was performed on stored bone marrow specimens of patients when the cytogenetic analysis showed CAs. During nilotinib therapy, 12 (92.3 %), 5 (38.5 %), and 2 (15.4 %) patients achieved complete cytogenetic response, major molecular response, and complete molecular response at 18 months, respectively. Two patients developed CAs in Ph- cells, including trisomy 8 and monosomies 20 and 21. Monosomies 20 and 21 appeared in the same patient simultaneously. Our data confirmed that clonal CAs in Ph- cells is a general phenomenon in Ph+ CML patient treated with tyrosine kinase inhibitors (TKIs), including nilotinib. The clinical significance of these CAs that arise in Ph+ CML patient treated with TKIs and whether these CAs exist before or after treatment of TKIs are not clear.
authors.affiliation: Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, Zhejiang, 310003, People's Republic of China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.forename: Yungui
authors.initials: Y
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D011743:Pyrimidines; D011505:Protein-Tyrosine Kinases; C498826:nilotinib