Clonal Relationship of Diagnosis and Relapse Samples in ALL. The majority of relapse cases have a clear relationship to the diagnosis leukemic clone, either arising through the acquisition of additional genetic lesions or, more commonly, arising from an ancestral (prediagnosis) clone. In the latter scenario, the relapse clone acquires new lesions while retaining some but not all of the lesions found in the diagnostic sample. Lesion-specific backtracking studies revealed that in most cases the relapse clone exists as a minor subclone within the diagnostic sample before the initiation of therapy. In only a minority of ALL cases does the relapse clone represent the emergence of a genetically distinct and thus unrelated second leukemia.From Mullighan CG, Phillips LA, Su X, et al. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science. 2008;322:1377-80. Reprinted with permission from AAAS.