Document Detail

Cytogenetic and fluorescence in situ hybridization monitoring in Ph+ Chronic Myeloid Leukemia patients treated with imatinib mesylate.
MedLine Citation:
PMID:  15354415     Owner:  NLM     Status:  MEDLINE    
Imatinib mesylate determines a favorable clinical course in most Ph positive Chronic Myeloid Leukemia (CML) patients in the chronic phase. Cytogenetic response is usually evaluated by analyzing 20-25 bone marrow metaphases using standard banding techniques. Since this methodology has very low sensitivity, we compared the results obtained by standard banding techniques to the ones obtained by fluorescent in situ hybridization (FISH). This was also done to identify any possible discrepancies between the two techniques. We analyzed 40 Ph+ CML patients in the chronic phase who had previously been treated with interferon alpha (IFNalpha) and who were receiving imatinib. The studies were performed by utilizing the same BM cell samples fixed in acetic acid/methanol, before imatinib therapy and then quarterly. Comparison of cytogenetic results to FISH results at 3 and 6 months of imatinib treatment showed that some patients who had achieved major cytogenetic response (i.e.<35% of examined metaphases showing Ph), showed retention of a higher number of persisting Ph+ cells when examined by FISH, and they did not achieve major FISH response (i.e. <35% of examined interphase cells show the BCR-ABL fusion signal). The discrepancy we found between the results that were obtained by analyzing metaphases and interphase cells disappeared in the subsequent examinations. Moreover, we found that 4 patients (10%) were still Ph+ in all the metaphases we examined even though they achieved excellent clinical response. On the basis of this small series of patients, we suggest that cytogenetic evaluation of patients on imatinib therapy should be performed by utilizing the classic banding technique (metaphase examination), but also by using the FISH technique (interphase examination), since the two methodologies may provide different results.
G Fugazza; M Miglino; R Bruzzone; S Quintino; A M Gatti; R Grasso; M Gobbi; F Frassoni; M Sessarego
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of experimental & clinical cancer research : CR     Volume:  23     ISSN:  0392-9078     ISO Abbreviation:  J. Exp. Clin. Cancer Res.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-09-09     Completed Date:  2005-01-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8308647     Medline TA:  J Exp Clin Cancer Res     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  295-9     Citation Subset:  IM    
Dipartimento di Medicina Interna and Dipartimento di Ematologia e Oncologia, Università degli Studi di Genova, Genova.
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MeSH Terms
Antineoplastic Agents / therapeutic use*
Bone Marrow / metabolism,  pathology
Chromosome Banding
Cytogenetic Analysis
Drug Resistance, Neoplasm
In Situ Hybridization, Fluorescence
Interferon-alpha / adverse effects
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*,  genetics,  pathology
Middle Aged
Neoplasm Recurrence, Local / drug therapy,  genetics,  pathology
Neoplasm, Residual / diagnosis*
Piperazines / therapeutic use*
Protein-Tyrosine Kinases / antagonists & inhibitors
Pyrimidines / therapeutic use*
Salvage Therapy
Survival Rate
Reg. No./Substance:
0/Antineoplastic Agents; 0/Interferon-alpha; 0/Piperazines; 0/Pyrimidines; 152459-95-5/imatinib; EC Kinases

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