Document Detail

The emergence of Ph-, trisomy -8+ cells in patients with chronic myeloid leukemia treated with imatinib mesylate.
MedLine Citation:
PMID:  12901975     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To describe clinical and laboratory features of a cohort of patients with chronic myelogenous leukemia (CML) who developed Ph(-), trisomy 8(+) metaphases while on treatment with imatinib mesylate. PATIENTS AND METHODS: Conventional cytogenetics and triple-color interphase fluorescence in situ hybridization were used to identify 5 of 310 studied patients who, on follow-up analysis, had Ph(-), trisomy 8(+) cells while on therapy. RESULTS: None of the 5 patients had cytogenetic evidence of clonal evolution at the start of treatment with imatinib. All patients developed grade 3 or 4 neutropenia and thrombocytopenia during treatment. The emergence of Ph(-), trisomy 8(+) metaphases was seen at 3, 6, 13, 16, and 18 months from the start of treatment and was present at multiple time points. The maximum number of trisomy 8 metaphases ranged from 25 to 50%. Concomitantly, all patients had a profound suppression of Ph(+) cells (ranging from 0 to 65%) as well as the appearance of normal metaphases, ranging from 6 to 55%. None of the patients has shown clinical or hematologic signs of progression to a more advanced phase of CML. CONCLUSIONS: While on treatment with imatinib mesylate a small group (less than 5%) of patients with CML developed Ph(-) trisomy 8(+) clone associated with pancytopenia. None of the patients developed clinical or hematological signs of progression to a more advanced phase of CML. These observations suggest that identification of trisomy 8 cells may represent clonal Ph(-) cells that were uncovered by treatment with a selective and potent inhibitor of Ph(+) cells.
Eric Feldman; Vesna Najfeld; Michael Schuster; Gail Roboz; Amy Chadburn; Richard T Silver
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental hematology     Volume:  31     ISSN:  0301-472X     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-08-06     Completed Date:  2003-09-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  702-7     Citation Subset:  IM    
The Leukemia and Myeloproliferative Center, Weill Medical College of Cornell University, New York, NY, USA.
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MeSH Terms
Antineoplastic Agents / adverse effects,  therapeutic use*
Chromosomes, Human, Pair 8
Clone Cells / pathology
Enzyme Inhibitors / adverse effects,  therapeutic use*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy,  genetics,  pathology*
Middle Aged
Pancytopenia / chemically induced
Philadelphia Chromosome
Piperazines / adverse effects,  therapeutic use*
Pyrimidines / adverse effects,  therapeutic use*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Piperazines; 0/Pyrimidines; 152459-95-5/imatinib
Comment In:
Exp Hematol. 2005 Feb;33(2):151   [PMID:  15676207 ]

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