Expression of thrombospondin receptor (CD36) in B-cell chronic lymphocyticleukemia as an indicator of tumor cell dissemination

Background and Objective. The expression of CD36 antigen has not been concl usively associated with human B-lymphocytes although CD36 was recently dete cted in a human a-cell angiotropic lymphoma where it might be involved in l ymphoblast-endothelial cell adhesion. We investigated the expression of CD3 6 in B-cell chronic lymphocytic leukemia (CLL) by multiparameter flow cytom etry; results were correlated with clinical features. Design and Methods. CD36 expression was evaluated on peripheral blood and b one marrow samples from 24 patients affected by CD5(+) B-CLL. Mononuclear c ells were isolated by Ficoll-Hypaque density gradient centrifugation, were labeled with fluorochrome-conjugated monoclonal antibodies under standard e xperimental conditions and were analyzed by flow cytometry. CD36 expression was quantified both in terms of frequency of CD19(+)CD36(+) cells and of m ean fluorescence intensity (MFI-R) of CD36(+) cell populations. The intensi ty of CD36 expression was arbitrarily classified as weak (MFI-R ranging fro m 3 to 6; score 0), moderate (MFI-R ranging from 6 to 9; scare 1), intermed iate (MFI-R ranging from 9 to 11; score 2) or strong (MFI-R ranging from 11 to 17; score 3). Results. CD36 could be detected on 3% (range 2-5) of normal CD19(+) B-lymph ocytes and on 45% (range 30-75) of neoplastic CD19(+) B-cells. When CLL pat ients were stratified according to CD36 staining intensity, higher hemoglob in levels (Hb) were recorded in patients assigned to score 0 (Hb = 14.3 g/d L; range 13.9-15.1) compared to patients scoring 1-2 (Hb = 11.2; range 10.3 -12.2) or 3 (Hb = 9.8; range 9.6-11.6; p=0.0053). similarly, higher platele t counts (Plt) were found in patients scoring 0 (Plt = 282x10(3)/mu L; rang e 244-319), compared to patients with intermediate (Plt =175x10(3)/mu L; ra nge 144-238) and high scores (Plt = 149x10(3)/mu L; range 103-230; p=0.044) ; lymphocyte count (Ly) was significantly higher in patients assigned to sc ore 3-4 (Ly = 23.3x10(3)/mu L, range 13-30) compared to score 0-2 (Ly = 9.8 x10(3)/mu L, range 8.5-10.8; p=0.045). CLL patients expressing CD36 at inte rmediate-to-strong intensity (MFI-R = 14, range 9-16) were more frequently assigned to Rai stages III-IV than stages I-II (CD36 MFI-R = 9, range 6.5-1 1; p=0.005) and stage 0 (CD36 MFI-R = 6, range 47.3; p<0.001). Interestingl y, bone marrow diffuse histology was strongly associated with higher CD36 e xpression (MFI-R = 8.7; range 4.7-13.9) compared to non-diffuse patterns of bone marrow Infiltration (MFI-R = 6.7; range 5.2-9.3; p=0.0019). In multiv ariate regression analysis, CD36 staining intensity significantly and indep endently correlated with diffuse BM histology (p=0.033). Interpretation and Conclusions. The present report provides the first evide nce of CD36 expression on CD19(+) B-cells from CLL; the correlations with c linical parameters strongly support the view that CD36 might favor tumor ce ll spreading. Whether high CD36 expression levels on CLL CD19(+) B-cells id entify an aggressive disease subset remains to be further confirmed in larg er series of patients. (C)1999, Ferrata Storti Foundation.