Expression of FLIP(Long) and FLIP(Short) 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-1beta-converting enzyme)-inhibitory protein)) was identified as an inhibitor of FAS and TRAIL signals. Here, we characterized FLIP(Long) (FLIP(L)) and FLIP(Short) (FLIP(S)) 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, FLIP(L) levels were higher among normal individuals than in MDS patients (P=0.04). Among total BMMNC, FLIP(L) levels also tended to be higher in normal subjects than in MDS patients, although this difference was not significant (P=0.71). FLIP(L) levels in CD34+ cells were negatively correlated with apoptosis in both normal and MDS marrows (P=0.03). FLIP(Short) 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 FLIP(L), FLIP(St) 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 FLIP(L) and FLIP(S) are differentially regulated, and that the relative levels of both isoforms play a role in the regulation of apoptosis in MDS.
Benesch
M
M
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Platzbecker
U
U
Ward
J
J
Deeg
H J
HJ
Leisenring
W
W
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D018922:HL-60 Cells; D006801:Humans; D016130:Immunophenotyping; D047908:Intracellular Signaling Peptides and Proteins; D007536:Isomerism; D019169:Jurkat Cells; D020014:K562 Cells; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology* / Q000503:physiopathology*; D020298:U937 Cells
D018952:Antigens, CD34; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins