Cytofluorimetric and functional analysis of c-kit receptor in acute leukemia

The SR-1 monoclonal antibody (MoAb) recognizes an epitope of the c-kit receptor (KR), present on normal hemopoietic CD34+ stem cells as well as on blasts from patients with acute leukemia. Cytometric analysis by indirect immunofluorescence with the SR-1 MoAb was performed in 98 patients with acute myeloblastic leukemia (AML) and in 37 patients with acute lymphoblastic leukemia (ALL) in order to detect the presence of the KR and to examine its prognostic significance. Sixty-nine of 98 (70%) AML patients were SR-1 positive independently of the FAB subtype, although a higher incidence of SR-1 positive cases was observed in M4 and M5 AML and in those cases that also coexpressed lymphoid antigens. Fourteen AML samples were studied by Northern blot analysis and the KR mRNA was detected in the majority of SR-1 positive cases and also in 2 of 3 SR-1 negative samples. Furthermore, "in vitro" cultures from 15 cases showed that recombinant human Stem cell factor (rhSCF) induced an increased proliferative activity in most tested cases (11/15); this was further enhanced when rhSCF was combined with rhIL-3 + rhGM-CSF (p = 0.007) and with the GM-CSF/IL-3 fusion protein PIXY321 (p = 0.003). Thirty-seven ALL cases were also studied and all but one were SR-1 negative. Interestingly, the only SR-1 positive case also coexpressed myeloid antigens and showed an "in vitro" response when stimulated with rhSCF. Finally, the complete remission (CR) rate, survival and event-free survival were evaluated in 75 AML patients who received standard and identical chemotherapy; unlike previous studies which utilized a different anti-KR MoAb (YB5.B8) and which showed a poor prognosis for KR positive patients, we were unable to document any significant difference in CR rate, survival and event-free survival.