Expression of the c-kit molecule in acute myeloid leukemias : implications of the immunophenotypes cd117 and cd15 in the detection of minimal residual disease,

Abstract EN

Objectives : study of the c-kit proto-oncogene (CD117) may be of help for the identification of phenotypic profiles that are absent or present at very low frequencies on normal human blast cells and therefore might be of great value for the detection of leukemic cells displaying such im-munophenotypes in patients in complete remission.

Design and methods : Ninety patients with acute mye-loid leukemias, diagnosed according to FAB criteria and immunological marker studies, were studied for the dual expression on blast cells of the CD117 / CD15 immuno-phenotype coexpression by direct immunofluorescence assay using dual staining combination flow cytometry.

Results: In 69 / 90 acute myeloid leukemia patients analyzed (77 %) ; blast cells expressed the CD117 antigen.

Moreover, in 38 of them (42 % of acute myeloid leukemia cases), leukemic blasts coexpressed the CD117 and CD15 antigens.

There was no significant correlation between the FAB classification and the CD117 and CD15 expression in acute myeloid leukemia cases.

Conclusions : these results suggest that immunological methods for the detection of MRD based on the existence of aberrant phenotypes could be used in the majority of AML patients.

This phenotype CD117 / CD15, present in acute myeloid leukemia cases at a relatively high frequency (42 %), represents an aberrant phenotype, because it was not detected on normal human blast cells, suggesting that the use of these combinations of monoclonal antibodies could be of help in detecting residual leukemic blasts among normal blast cells.

The use of the CD117 antigen in different monoclonal antibodies combinations may be of great help for the detection of minimal residual disease in a high proportion of acute myeloid leukemia cases, especially in those patients displaying the CD117+ / CD15+ im-munophenotype, because cells coexpressing both antigens in normal blasts, if present, are at very low frequencies.

The simultaneous assessment of two or more markers in single cells has facilitated the identification of multiple aberrant phenotypes which should permit the detection of impending relapses prior to clinical manifestations; MRD testing in patients with AML in clinical remission is a potentially useful tool for assessing the risk of relapse and guiding therapeutic decisions.

The detection of MRD before overt relapse may provide information for early intervention, while definitive recognition of normal recovering blasts may prevent unnecessary treatment.