L-selectin expression is low on CD34+ cells from patients with chronic myeloid leukemia and interferon-a up-regulates this expression.
OBJECTIVE
Altered adhesive interaction between bone marrow (BM) stroma and progenitors in chronic myeloid leukemia (CML) may be in part caused by abnormal expression of cell adhesion molecules (CAMs) on malignant progenitor cells. Treatment of CML with interferon-a (IFN-a) re-establishes normal hemopoiesis in some patients in part by restoring normal adhesive interactions between CML progenitors and BM microenvironment, which may in turn be mediated by correcting CAM expression on progenitors.


METHODS
We investigated the expression of CAMs (L-selectin, b((2))-integrin, LFA-3, ICAM-1, ICAM-3, NCAM) on purified BM CD34(+) cells from CML patients (n= 34) and healthy adults (n= 15) by flow cytometry. Modulation of L-selectin expression on CD34(+) cells from CML after in vitro treatment with IFN-a was also investigated.


RESULTS
The mean percentage of CD34(+ )cells expressing L-selectin was significantly lower in CML patients (25.4+/-12.8%) than in normal controls (68.7+/-8.3%, n=15). CD34(+)/HLA-DR(&endash;/low) and CD34(+)/ CD38(&endash;/low) co-expressing L-selectin were also significantly lower in untreated CML (27.4+/-21.5% and 39.8+/-26.7%, respectively, n=8) than in controls (61+/-17% and 83.7+/-10%, respectively, n=7). In vitro treatment with IFN-a of purified CD34(+) BM cells from untreated CML patients (n=8) induced a significant, dose and time-dependent increase in the L-selectin expression as indicated by FACS analysis.


CONCLUSIONS
We hypothesize that this L-selectin deficiency reflects a cell surface adhesion defect of progenitors from CML that is partially restored by in vitro IFN-a treatment. These data may help to explain the adhesive abnormalities of CML progenitors to the BM microenvironment and the in vitro restoration of adhesion capacity after IFN-a treatment.
Martín-Henao
G A
GA
Department of Cryobiology and Cell Therapy, Cancer Research Institute, Hospital Duran i Reynals, Av. Castelldefels, Km 2.7, L'Hospitalet de Llobregat, 08907 Barcelona, Spain. gmartinh@iro.es.
Quiroga
R
R
Sureda
A
A
González
J R
JR
Moreno
V
V
García
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D019041:L-Selectin / Q000096:biosynthesis*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D016898:Interferon-alpha; D019041:L-Selectin