Expression of FLIPLong and FLIPShort in bone marrow mononuclear and CD34+ cells in patients with myelodysplastic syndrome: correlation with apoptosis

Several apoptosis-inducing systems, including Fas/Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) and its receptors, are upregulated in myelodysplastic syndrome (MDS). FLIP (FLICE (FAS-associated death-domain-like IL-1β-converting enzyme)-inhibitory protein)) was identified as an inhibitor of FAS and TRAIL signals. Here, we characterized FLIPLong (FLIPL) and FLIPShort (FLIPS) expression in bone marrow mononuclear cells (BMMNCs) and in CD34+ cells of 29 MDS patients, and in 17 normal volunteers. The expression was correlated with apoptotic indices. In CD34+ cells, FLIPL levels were higher among normal individuals than in MDS patients (P=0.04). Among total BMMNC, FLIPL levels also tended to be higher in normal subjects than in MDS patients, although this difference was not significant (P=0.71). FLIPL levels in CD34+ cells were negatively correlated with apoptosis in both normal and MDS marrows (P=0.03). FLIPShort RNA expression was higher in MDS patients than in normal controls in both BMMNC (P=0.03) and CD34+ cells (P=0.08). In contrast to FLIPL, FLIPSt levels were positively correlated with apoptosis. At the protein level FLIP was most readily detectable in patients with high blast counts. The data suggest that FLIPL and FLIPS are differentially regulated, and that the relative levels of both isoforms play a role in the regulation of apoptosis in MDS.