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Abnormal expression of N-CAM (CD56) adhesion molecule on myeloid and progenitor cells from chronic myeloid leukemia
1LRF Centre for Adult Leukaemia, RPMS, Hammersmith Hospital, London, UK.
Insights
CD56 is aberrantly expressed on myeloid cells in chronic myelogenous leukemia (CML), unlike in healthy donors. This CD56 expression may impact disease spread and can serve as a marker for monitoring CML relapse after transplantation.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML) is a myeloproliferative neoplasm.
- The aberrant expression of cell surface markers can provide insights into CML pathogenesis and progression.
Purpose of the Study:
- To investigate the expression of CD56 on myeloid cells in patients with Ph+ CML.
- To determine the clinical significance of CD56 expression in CML.
Main Methods:
- Flow cytometry and immunocytochemistry were used to detect CD56 expression on bone marrow and peripheral blood cells from 36 CML patients and healthy donors.
- CD56+ cells were analyzed for coexpression with CD34 and functional assays (CFU-GM) were performed.
Main Results:
- CD56 was expressed on myeloid cells in 19 out of 36 CML patients (12-77%), but not in healthy donors.
- CD56 expression increased with myeloid differentiation and was higher in peripheral blood than bone marrow.
- CD56+ CML cells coexpressed CD34, and alpha interferon treatment reduced CD56 expression and Ph positivity.
Conclusions:
- CD56 expression on CML myeloid cells is an aberrant phenomenon potentially affecting cell homing and dissemination.
- CD56 detection can serve as a marker for monitoring CML patients, with reappearance indicating early relapse post-transplantation.
Abstract:
Bone marrow and peripheral blood samples from 36 patients with Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML) (30 in chronic phase, four in accelerated phase, and two in blastic crisis) were tested with two CD56 monoclonal antibodies (My31 and Eric 1) using the Facscan flow cytometer. Two- and three-color fluorescence experiments 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 (BM) of healthy donors. Immunocytochemical staining (APAAP technique) of CML peripheral blood (PB) and BM slides showed that CD56 expression was detectable from the myelocyte stage with the strongest staining in the metamyelocyte stage. Neutrophils were negative both by flow cytometry and APAAP analysis. In individual CML patients, an increasing number of CD56+ cells were recovered with progressively higher density cuts (1.065-1.077 g/ml), supporting the concept that the antigen level tends to increase during myeloid differentiation. Furthermore, 19% of CML patients coexpressed CD56 and CD34 antigens in 10-45% of the CD34+ cells. 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 that the CD56 expression was brighter and the number of positive cells significantly higher in the peripheral blood myeloid cells as compared to their 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 conclusion, the expression of CD56 on CML myeloid elements seems to represent an aberrant phenomenon which could affect the cell homing mechanisms and, probably, the pattern of tumor cell dissemination. In patients with CD56+ CML, its detection could be further used as a means of monitoring patients undergoing bone marrow transplantation, since its reappearance is associated with early relapse of the disease.