Leukemia relapse reconsidered from the molecular aspect

Relapse, a major obstacle in the treatment of acute leukemia, is essentiall y caused by re-growth of residual leukemia cells, frequently accompanied by resistance to chemotherapy. Comparative studies of clones both at initial diagnosis and at subsequent relapse have indicated that phenotype and karyo type are frequently changed at relapse. This can be recognized as the resul t of negative selection by chemotherapy in a heterogeneous population. Furt hermore, complex molecular alterations that include the loss of as well as the acquisition of mutations are noticed bq comparing multiple genes associ ated with leukemia, suggesting a continuous genetic evolution. Studies on l eukemia relapse have thus served as a model of clonal progression, which ca n be serially observed, including selection by chemotherapy, induction of r esistant phenotype, and genetic alteration.