Differential expression of very late activation antigen-3 (VLA-3)/VLA-4 in B-cell non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia

Abstract

The expression of beta 1 (very late activation antigens, VLA 1–6) and beta 2 integrins (leukocyte adhesion molecules [Leu-CAM]) in cell suspensions from the peripheral blood of 70 patients with B-cell chronic lymphocytic leukemia (B-CLL), 15 patients with leukemic lymphocytic lymphoma of intermediate differentiation (IDL), as well as from the lymph nodes of 20 patients with low/intermediate-grade non- Hodgkin's lymphoma (NHL) was studied with the aim of characterizing their adhesive phenotype and evaluating its relationship to clinical behavior. CD11a(LFA-1) was more expressed in NHL and IDL than in B-CLL (P = .047), although it was demonstrable in 74.2% of cases; CD11c was more expressed in B-CLL (P less than .0001), and its expression was preserved in almost all of the cases of small lymphocytic lymphoma. In NHL patients, including the cases of IDL, VLA-3 expression was observable in 8 of 35 cases (although always at a low level of intensity), while VLA-4 was almost constantly expressed in a way that was similar to its expression in control normal B cells. On the contrary, in B-CLL patients, VLA-3 was expressed (prevalently at high levels) in 87.1% of cases and VLA-4 only in 37.1%. No correlation was found between adhesion molecule patterns and the clinical features of the diseases. The biofunctional significance of the imbalance of VLA-3 and VLA-4 expression in B-CLL is not easy to explain, but it has undoubted intrinsic value as an additional marker for distinguishing B- CLL from, in particular, those B-cell neoplasms (such as IDL) that share many of the immunocytomorphologic characteristics and the putative normal counterpart (the mantle zone) of B-CLL.

Signature of B‐CLL with different prognosis by Shrunken centroids of surface antigen expression profiling

“…Regarding other b1-integrins, whereas expression of CD49a, CD49b, and CD49f was mainly negative (Baldini et al, 1992) also in our B-CLL series, supervised analysis selected the overexpression of CD49d, usually in association with the above-average expression of CD38, CD29, and CD49e, as a part of the signature identifying one of the two B-CLL subgroups with worse prognosis (group II). This finding is in keeping with a recent report on B-CLL gene expression profiling (Pittner et al, 2003), in which, high levels of CD49d mRNA were found to be part of the signature distinguishing CD38 þ from CD38 -B-CLL cells (Crespo et al, 2003;Gattei et al, 2003;McCarthy et al, 2003;Oppezzo et al, 2003;Degan et al, 2004a;Orchard et al, 2004;Rassenti et al, 2004).…”

An aggressive subtype of B‐CLL is characterized by strong CD44 expression and lack of CD11c

“…Lacking or low expression of CD11a in B-CLL and NHL (Inghirami et al, 1988;Caligaris-Cappio et al, 1989) was supposed to influence the growth pattern of lymphoma. However, further studies (De Rossi et al, 1993;Baldini et al, 1992;Terpe et al, 1994;Stauder et al, 1989) did not corroborate this hypothesis. Our finding that CD11a (LFA-1) is commonly expressed in B-CLL but not related to clinical course and prognosis is in agreement with the later observations.…”

“…Adhesion molecules, such as CD44 and its variant isoforms and integrins, are known to play a pivotal role in cell-cell and cell-stroma interactions involved in proliferation, spread via blood and lymph vessels, tumour invasion and metastasis (Roosien et al, 1989;Hynes, 1992;Gü nthert et al, 1991;Lesley et al, 1993;Ruoslahti & Giancotti, 1989;Stauder & Gü nthert, 1955). Their expression has been widely investigated in lymphoproliferative diseases ( Jalkanen et al, 1991;Baldini et al, 1992;Pals et al, 1989;Terpe et al, 1994;Horst et al, 1990). Whereas CD44 has been shown to correlate with prognosis mainly in diffuse-large cell lymphoma ( Jalkanen et al, 1990( Jalkanen et al, , 1991Pals et al, 1989;Horst et al, 1990;reviewed in Gü nthert et al, 1995), in B-CLL no clear-cut correlation on the prognostic relevance of CD44 expression could be demonstrated (Baldini et al, 1992;Pals et al, 1989;Jalkanen et al, 1990;Erikstein et al, 1993;De Rossi et al, 1993).…”

“…Their expression has been widely investigated in lymphoproliferative diseases ( Jalkanen et al, 1991;Baldini et al, 1992;Pals et al, 1989;Terpe et al, 1994;Horst et al, 1990). Whereas CD44 has been shown to correlate with prognosis mainly in diffuse-large cell lymphoma ( Jalkanen et al, 1990( Jalkanen et al, , 1991Pals et al, 1989;Horst et al, 1990;reviewed in Gü nthert et al, 1995), in B-CLL no clear-cut correlation on the prognostic relevance of CD44 expression could be demonstrated (Baldini et al, 1992;Pals et al, 1989;Jalkanen et al, 1990;Erikstein et al, 1993;De Rossi et al, 1993). Integrins are a diverse family of heterodimeric intercellular and cell-matrix adhesion receptors (Arnaout, 1990).…”

The clinical and biological features of a series of immunophenotypic variant of B‐CLL

“…Mononuclear cell suspensions were obtained from heparinised peripheral blood by means of Ficoll-Hypaque gradient centrifugation. The samples underwent direct immunofluorescence staining with monoclonal antibodies (MoAbs), and the surface immunoglobulins (SIg) were characterised as previously described (12). The MoAbs used were CD45-PerCP, CD10-FITC; CD5-FITC, CD19-PerCP, CD20-PE, CD23-PE, CD11c and CD38-PE (Becton Dickinson, Mountain View, CA, USA); CD43-FITC and CD49d (Immunotech SA, Marseilles, France); CD1c-FITC (Ancell Corporation, Bayport, MN, USA); CD103-FITC (Immuno Quality products, Groningen, The Netherlands); and FMC7-FITC and CD79b-FITC (DAKO, Glostrup, Denmark).…”