Quantitative characterization and potential function of membrane Fas/APO‐1 (CD95) receptors on leukaemic cells from chronic B and T lymphoid leukaemias

Abstract

Summary.The expression and function of the Fas-receptor (Fas-R) were examined in chronic lymphocytic leukaemia (CLL), hairy cell leukaemia-variant (HCL-v) and adult T-cell leukaemia (ATL). The expression of Fas-R in freshly isolated leukaemic cells was qualitatively and quantitatively different between each disease; faint in B-CLL, moderate in HCL-v and strong in ATL. Both full-length and alternatively spliced truncated forms of Fas mRNA were detected even in CLL B cells with faint to negative Fas-R, and Fas mRNA was also shown to be capable of increasing in vitro expression, i.e. the message was functional. In contrast, Fas-R expression on ATL cells was heterogenous and usually intense with a mean density approximately 3-fold higher than that of normal T cells. Fas-R was confirmed to have the potential function for anti-Fas monoclonal antibody-mediated cell death in vitro in Fas-R þ ATL cells. The expression level of Fas-R on the cells was higher in chronic than acute ATL (10360 v 6260 antibody-binding capacity per cell, mFas ABC ; P < 0·05) and was inversely correlated with serum LDH activity, suggesting that the strong Fas-R accounts for the slow progression of chronic ATL and the negative Fas-R protects from Fasmediated cell death. These results show that Fas-R expression on leukaemic cells is valuable in their characterization and perhaps their function, and may contribute to the progression and immune evasion of malignant clones.

Evidence for distinct pathomechanisms in B-cell chronic lymphocytic leukemia and mantle cell lymphoma by quantitative expression analysis of cell cycle and apoptosis-associated genes

“…Quantitative studies in MCL revealed overexpression of cyclin D1 22,23 and MYC. 24 In B-CLL faint expression of CD95 (TNFSF6) and CD95-R (TNFRSF6), 5,25 overexpression of BCL2, steady-state expression of TP53, and decreased expression of BAX in progressive disease were reported. 26 To obtain a comprehensive view of the activated or deregulated factors and pathways with oncogenic potential, we analyzed a series of MCL and B-CLL samples for expression of the following genes, which were selected based on their localization in altered genomic regions or on the function of their products in cell cycle and apoptosis control: ATM, BAX, BCL2, CCND1, cyclin D3 (CCND3), CDK2, CDK4, p21 (CDKN1A), p27 (CDKN1B), E2F1, ETV5, MYC, RB1, L-selectin (SELL), DP2 (TFDP2), TRAIL (TNFSF10), and TP53.…”

Clinical and oncological significance of aberrant Fas (APO-1/CD95) isoform expression in adult T-cell leukemia

“…To understand these issues, it is convenient to examine our mFas-r.~gative ATL cells. First of all, it has been demonstarted that the ATL cells preserve normally both full-length and truncated Fas mRNAs, corresponding to mFas and sFas receptors (20,25,26). Indeed, de novo fresh mFasnegative ATL cells come to express detectable mFas along with the change to dominant expression of the full-length mRNA and decrease of the truncated mRNA (Fig.…”

“…In this paper, we review clinical and oncological significance of quantitatively and qualitatively aberrant expression of the membrane and soluble isoforms of Fas in ATL on the basis of our recent studies published elsewhere (20,(25)(26)(27).…”

“…ATL is derived from an uncontrolled clonal expansion of T-cells, probably via transactivation mechanisms of pX gene products of human T-cell leukemia virus type-1 (HTLV-1) integrated into the genome Like IL-2R, which is highly expressed on ATL cells due to transactivation by pX proteins (22,23), mFas is also abundantly expressed (24,25), however despite up-regulation of mFas, the cells can survive and form tumours which are associated with extremely poor prognosis. Recently, we have in vivo via its decoy function, the serum sFas level also should be considered to understand the Fasmediated apoptosis in blood.…”

Surface membrane antigen expression changes induced in vitro by exogenous growth factors in chronic lymphocytic leukemia cells

“…These include, for instance, IL-2 receptor components (CD25, CD122 and CD132), 7 IL-4 receptor (CD124), 8,9 IL-6 receptor (CD126), 9 as well as tumor necrosis factor receptor superfamily members, such as CD30, 10 CD40 11-13 and CD95. [14][15][16] In addition to the data accumulated concerning their biochemical actions and cellular functions, some interesting clinical aspects of several membrane antigens are emerging. The marked heterogeneity in the clinical course of patients with apparently similar features can be explained by variable expression of regulatory molecules.…”