Must the last CML cell be killed?

Do we have to kill the last CML cell? DM Ross, TP Hughes and JV Melo, Leukemia 2010(Sep 16) [Epub ahead of print][FriendFeed entry][PubMed citation][Full text]. The abstract of this OA review:

Previous experience in the treatment of chronic myeloid leukaemic (CML) has shown that the achievement of clinical, morphological and cytogenetic remission does not indicate eradication of the disease. A complete molecular response (CMR; no detectable BCR-ABL mRNA) represents a deeper level of response, but even CMR is not a guarantee of elimination of the leukaemic, because the significance of CMR is determined by the detection limit of the assay that is used. Two studies of imatinib cessation in CMR are underway, cumulatively involving over 100 patients. The current estimated rate of stable CMR after stopping imatinib is approximately 40%, but the duration of follow-up is relatively short. The factors that determine relapse risk are yet to be identified. The intrinsic capacity of any residual leukaemic cells to proliferate following the withdrawal of treatment may be important, but there may also be a role for immunological suppression of the leukaemic clone. No currently available test can formally prove that the leukaemic clone is eradicated. Here we discuss the sensitive measurement of minimal residual disease, and speculate on the biology of BCR-ABL-positive cells that may persist after effective therapy of CML.

Clonal origins of relapsed ALL

Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia by Charles G Mullighan and 6 co-authors, including James R Downing, Science 2008(Nov 28); 322(5906): 1377-80. PubMed Abstract:

Most children with acute lymphoblastic leukemia (ALL) can be cured, but the prognosis is dismal for the minority of patients who relapse after treatment. To explore the genetic basis of relapse, we performed genome-wide DNA copy number analyses on matched diagnosis and relapse samples from 61 pediatric patients with ALL. The diagnosis and relapse samples typically showed different patterns of genomic copy number abnormalities (CNAs), with the CNAs acquired at relapse preferentially affecting genes implicated in cell cycle regulation and B cell development. Most relapse samples lacked some of the CNAs present at diagnosis, which suggests that the cells responsible for relapse are ancestral to the primary leukemia cells. Backtracking studies revealed that cells corresponding to the relapse clone were often present as minor subpopulations at diagnosis. These data suggest that genomic abnormalities contributing to ALL relapse are selected for during treatment, and they point to new targets for therapeutic intervention.