In search of the original leukemic clone in chronic myeloid leukemia patients in complete molecular remission after stem cell transplantation or imatinib

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), 1329-1335. (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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Contributors

Author: Nicholas C.P. Cross

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