Document Detail


In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular remission after stem cell transplantation or imatinib.
MedLine Citation:
PMID:  20462961     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It is not clear if absence of BCR-ABL transcripts--complete molecular response (CMR)--is synonymous with, or required for, cure of chronic myeloid leukemia (CML). Some patients achieve CMR with imatinib (IM), but most relapse shortly after treatment discontinuation. Furthermore, most patients in long-term remission (LTR) post-stem cell transplantation (SCT) are considered functionally cured, although some remain occasionally positive for low-level BCR-ABL mRNA. Interpretation of the latter is complicated because it has been observed in healthy subjects. We designed a patient-specific, highly sensitive, DNA quantitative polymerase chain reaction to test follow-up samples for the original leukemic clone, identified by its unique genomic BCR-ABL fusion (gBCR-ABL). In 5 IM-treated patients in CMR, gBCR-ABL was detected in transcript-negative samples; 4 patients became gBCR-ABL-negative with continuing IM therapy. In contrast, of 9 patients in LTR (13-27 years) post-SCT, gBCR-ABL was detected in only 1, despite occasional transcript-positive samples in 8 of them. In conclusion, in IM-treated patients, absence of transcripts should not be interpreted as absence of the leukemic clone, although continuing IM after achievement of CMR may lead to further reduction of residual disease. Post-SCT, we found little evidence that the transcripts occasionally detected originate from the leukemic clone.
Authors:
Manuel Sobrinho-Simões; Vicki Wilczek; Joannah Score; Nicholas C P Cross; Jane F Apperley; Junia V Melo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-12
Journal Detail:
Title:  Blood     Volume:  116     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-27     Completed Date:  2010-09-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1329-35     Citation Subset:  AIM; IM    
Affiliation:
Department of Haematology, Imperial College London, London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antineoplastic Agents / therapeutic use*
Combined Modality Therapy
Female
Fusion Proteins, bcr-abl / genetics
Graft vs Host Disease / genetics,  prevention & control
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis,  genetics,  therapy*
Male
Middle Aged
Neoplasm Recurrence, Local / diagnosis,  genetics,  therapy*
Neoplasm, Residual / diagnosis,  genetics,  therapy*
Piperazines / therapeutic use*
Pyrimidines / therapeutic use*
RNA, Messenger / genetics
Remission Induction
Reverse Transcriptase Polymerase Chain Reaction
Sensitivity and Specificity
Stem Cell Transplantation*
Young Adult
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Fusion Proteins, bcr-abl; 0/Piperazines; 0/Pyrimidines; 0/RNA, Messenger; 152459-95-5/imatinib
Comments/Corrections
Comment In:
Blood. 2010 Aug 26;116(8):1192   [PMID:  20798240 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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