ABNORMAL EXPRESSION OF N-CAM (CD56) ADHESION MOLECULE ON MYELOID AND PROGENITOR CELLS FROM CHRONIC MYELOID-LEUKEMIA

Bone marrow and peripheral blood samples from 36 patients with Philade lphia chromosome positive chronic myelogenous leukemia (Ph+ CML) (30 i n chronic phase, four in accelerated phase, and two in blastic crisis) were tested with two CD56 monoclonal antibodies (My31 and Eric 1) usi ng the Facscan flow cytometer. Two- and three-color fluorescence exper iments indicated that CD13+ /CD33+ myeloid cells from 19 out of the 36 patients were positive for CD56 in 12-77% of the cells. In contrast, no CD56 positivity was documented in myeloid cells from bone marrow (B M) of healthy donors. Immunocytochemical staining (APAAP technique) of CML peripheral blood (PB) and BM slides showed that CD56 expression w as detectable from the myelocyte stage with the strongest staining in the metamyelocyte stage. Neutrophils were negative both by flow cytome try and APAAP analysis. In individual CML patients, an increasing numb er of CD56+ cells were recovered with progressively higher density cut s (1.065-1.077 g/ml), supporting the concept that the antigen level te nds to increase during myeloid differentiation. Furthermore, 19% of CM L patients coexpressed CD56 and CD34 antigens in 10-45% of the CD34+ c ells. The myeloid nature of CD56+/CD34+ CML cells has been ascertained by granulocyte-macrophage colony-forming unit (CFU-GM) assays on CD56 + cells sorted on FACS. Furthermore, in six out of eight CML patients in whom we performed a comparative BM and PB analysis, we found thal t he CD56 expression was brighter and the number of positive cells signi ficantly higher in the peripheral blood myeloid cells as compared to t heir BM counterpart. In short-term liquid cultures, low doses (50 U/ml ) of alpha interferon down-regulated the CD56 expression in CML cells, accompanied by a significant reduction of the Ph positivity. In concl usion, the expression of CD56 on CML myeloid elements seems to represe nt an aberrant phenomenon which could affect the cell homing mechanism s and, probably, the pattern of tumor cell dissemination. In patients with CD56+ CML, its detection could be further used as a means of moni toring patients undergoing bone marrow transplantation, since its reap pearance is associated with early relapse of the disease.