Fas/Apo-1(CD95) expression and apoptosis in patients with myelodysplastic syndromes

Abstract

Apoptosis of hematopoietic progenitor cells is increased inFas (Apo-1/CD95) is a cell-surface protein. It belongs to the myelodysplastic syndromes (MDS). We have studied Fas tumor necrosis factor (TNF) and nerve growth factor (NGF) (CD95/Apo-1) antigen expression in 27 MDS patients (RARS 4, receptor superfamily. 6,7 Fas crosslinking by the Fas ligand or RA 3, RAEB 13; RAEB-t 3, CMML 4) and three AML secondary an agonist anti-Fas antibody can deliver a cell death signal. (FAB) committee criterias. These patients included four refrac-

Localization of Fas and Fas ligand in bone marrow cells demonstrating myelodysplasia

“…However, much fewer cells were evaluated as apoptotic based on morphology 23 or a TUNEL technique on bone marrow smears. 24,25 In the present study, we examined the apoptotic cells by the TUNEL method using frozen bone marrow samples and demonstrated that the mean percentage of apoptotic cells in the bone marrow of MDS was 17.2% which was comparable to the rate determined by TUNEL method using bone marrow smears. Although there are no clear explanations for the difference in the rate of apoptosis observed in various studies, the main difference may be ascribed to the fixation of bone marrow samples.…”

“…34 The number of FasL expressing bone marrow mononuclear cells of MDS patients was also increased com- pared to control bone marrow cells. 34 Recently, Bouscary et al 25 have shown that patients with MDS had upregulation of Fas expression on total bone marrow nuclear cells, CD34-positive, CD33-positive and glycophorin-positive bone marrow cells compared to controls. No statistical correlation could be found between Fas expression and apoptosis rate.…”

Mitochondria in hematopoiesis and hematological diseases

“…Whether these mutations are associated with abnormal oxidative phosphorylation measured in myelodysplastic syndrome bone-marrow samples is a matter of discussion (Bowen and Peddie, 2002;Matthes et al, 2002). At least in older patients, they could also play a role in excessive apoptosis that characterizes low-grade myelodysplastic syndromes (Bouscary et al, 1997) as mice with defective mtDNA polymerase exhibit apoptosis in excess in several rapidly growing tissues (Kujoth et al, 2005) and in vivo apoptosis is increased in cells lacking mtDNA (Wang et al, 2001).…”

“…At early stages of acquired myelodysplastic syndromes, exacerbation of the physiological pathway to caspase activation in erythroid cells, even in the presence of elevated Epo concentrations, is responsible for a high rate of apoptosis, ineffective erythropoiesis and increased phagocytosis (Raza et al, 1995;Bouscary et al, 1997;Hellstrom-Lindberg et al, 2001;Shetty et al, 2002;Tehranchi et al, 2003;Testa, 2004). Several observations argue for a role of the Fas-L/Fas pathway in this pathogenic event.…”

“…Several observations argue for a role of the Fas-L/Fas pathway in this pathogenic event. First, both the death receptor and its ligand are overexpressed at the surface of bonemarrow cells from patients with early-stage myelodysplastic syndrome, including immature CD34 þ hematopoietic progenitors and more differentiated erythroid and granulo-monocytic precursors (Gersuk et al, 1996;Bouscary et al, 1997;Kitagawa et al, 1998). Secondly, the Fas-mediated apoptotic pathway is functional in these cells as their Fas-dependent apoptosis can be triggered by an agonistic antibody (Claessens et al, 2002).…”