Clonal chromosomal abnormalities in the stem cell compartment of patients with acute myeloid leukemia in morphological complete remission

Acute myeloid leukemia arises from the clonal expansion of a malignant tran sformed progenitor cell. Despite intensive chemotherapy, final disease erad ication is achieved by a small proportion of cases only and 50-70% of adult s with AML will ultimately relapse and die from their disease. Hence residu al disease below the level of morphological detectability must be assumed i n clinical and morphological complete remission. CD34(+)/CD38(-) and CD34()/CD38(+) subpopulations of seven patients in morphological complete remiss ion were isolated by FAGS (purity >98%) and were analyzed by conventional c ytogenetics or FISH for chromosomal aberrations. In five of seven patients, clonal chromosomal abnormalities were detected in the CD34(+)/CD38(+) subp opulation and in one patient with AML M2 (add (2)(q37)) in the most immatur e CD34(+)/CD38(-) stem cell compartment. One patient with AML M4Eo (inv(16) ,+8), showed a normal karyotype by conventional cytogenetic analysis, where as four of 15 metaphases of the sorted CD34(+)/CD38(+) subpopulation reveal ed the inversion 16. These observations underline that leukemic cells can s urvive intensive chemotherapy in the niche of the stem cell compartment. In some patients the sensitivity for the detection of persistent leukemic cel ls seems to be higher in FAGS-sorted subpopulations than conventional cytog enetic analysis of the unseparated bone marrow. Immunophenotyping revealed minimal residual disease in four of the patients. Functional analysis has t o be performed to investigate the leukemogenic potential of these residual cells.