In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular remission after stem cell transplantation or imatinib
In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular remission after stem cell transplantation or imatinib
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 since it has been observed in healthy individuals. We designed a patient-specific, highly sensitive, DNA quantitative PCR 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, out 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.
1329-1335
Sobrinho-Simoes, Manuel
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Wilczek, Vicki
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Score, Joannah
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Cross, Nicholas C.P.
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Apperley, Jane F.
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Melo, Junia V.
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26 August 2010
Sobrinho-Simoes, Manuel
6ad6c74c-852b-4b0e-8fff-0cf4aafe57d9
Wilczek, Vicki
fc0e5dfb-97c1-437a-96d2-078714aeb799
Score, Joannah
ea0db6ef-c17e-4915-b216-ac67c07b26b7
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Apperley, Jane F.
bb44333d-1437-4eb8-876a-37332e9ffcbc
Melo, Junia V.
0e816e85-ca9f-4a79-9c6f-91ce2279694c
Sobrinho-Simoes, Manuel, Wilczek, Vicki, Score, Joannah, Cross, Nicholas C.P., Apperley, Jane F. and Melo, Junia V.
(2010)
In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular remission after stem cell transplantation or imatinib.
Blood, 116 (8), .
(doi:10.1182/blood-2009-11-255109).
Abstract
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 since it has been observed in healthy individuals. We designed a patient-specific, highly sensitive, DNA quantitative PCR 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, out 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.
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Published date: 26 August 2010
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Local EPrints ID: 153079
URI: http://eprints.soton.ac.uk/id/eprint/153079
ISSN: 0006-4971
PURE UUID: 9721f1ca-64bc-4ce8-be18-b2d70b6af4ea
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Date deposited: 18 May 2010 15:00
Last modified: 14 Mar 2024 02:46
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Author:
Manuel Sobrinho-Simoes
Author:
Vicki Wilczek
Author:
Joannah Score
Author:
Jane F. Apperley
Author:
Junia V. Melo
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