{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:53:21Z","timestamp":1791140001351,"version":"4.1.0"},"reference-count":55,"publisher":"American Society of Hematology","issue":"10","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Myelodysplastic syndromes (MDSs) are characterized by peripheral blood cytopenia including anemia. We have investigated the implication of the extrinsic pathway of apoptosis in MDS-ineffective erythropoiesis by in vitro expansion of erythroid precursors from early stage (low and intermediate-1 International Prognosis Scoring System [IPSS]) MDS, advanced stage (intermediate-2 IPSS) MDS, and control bone marrow samples. We have previously shown that Fas and its ligand were overexpressed in early stage MDS erythroid cells. Here, we show that caspase-8 activity is significantly increased, whereas the expression of death receptors other than Fas, including the type 1 receptor for tumor necrosis factor \u03b1 (TNF-\u03b1) and the receptors for the TNF-related apoptosis-inducing ligand (TRAIL), DR4 and DR5, was normal. We also observed that the adapter Fas-associated death domain (FADD) was overexpressed in early stage MDS erythroid cells. Transduction of early stage MDS-derived CD34+ progenitors with a FADD-encoding construct increased apoptosis of erythroid cells and dramatically reduced erythroid burst-forming unit (BFU-E) growth. Transduction of a dominant-negative (dn) mutant of FADD inhibited caspase-8 activity and cell death and rescued BFU-E growth without abrogating erythroid differentiation. These results extend the observation that Fas-dependent activation of caspase-8 accounts for apoptosis of early stage MDS erythroid cells and demonstrate for the first time that FADD is a valuable target to correct ineffective erythropoiesis in these syndromes.<\/jats:p>","DOI":"10.1182\/blood-2004-08-3166","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T01:33:47Z","timestamp":1106876027000},"page":"4035-4042","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":56,"title":["Rescue of early-stage myelodysplastic syndrome-deriving erythroid precursors by the ectopic expression of a dominant-negative form of FADD"],"prefix":"10.1182","volume":"105","author":[{"given":"Yann-Erick","family":"Claessens","sequence":"first","affiliation":[{"name":"From the Departement d'Hematologie, Institut Cochin, l'Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U567, Centre National de la Recherche Scientifique Unite\u0301 Mixtes de Recherche (CNRS UMR) 8104, Universite Rene-Descartes, Paris, France; INSERM U517, Faculte de Medecine, Dijon, France; and the Hopital Cochin, Assistance Publique-Ho\u0302pitaux de Paris (AP-HP), Service d'Hematologie, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Park","sequence":"additional","affiliation":[{"name":"From the Departement d'Hematologie, Institut Cochin, l'Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U567, Centre National de la Recherche Scientifique Unite\u0301 Mixtes de Recherche (CNRS UMR) 8104, Universite Rene-Descartes, Paris, France; INSERM U517, Faculte de Medecine, Dijon, France; and the Hopital Cochin, Assistance Publique-Ho\u0302pitaux de Paris (AP-HP), Service d'Hematologie, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Dubart-Kupperschmitt","sequence":"additional","affiliation":[{"name":"From the Departement d'Hematologie, Institut Cochin, l'Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U567, Centre National de la Recherche Scientifique Unite\u0301 Mixtes de Recherche (CNRS UMR) 8104, Universite Rene-Descartes, Paris, France; INSERM U517, Faculte de Medecine, Dijon, France; and the Hopital Cochin, Assistance Publique-Ho\u0302pitaux de Paris (AP-HP), Service d'Hematologie, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Mariot","sequence":"additional","affiliation":[{"name":"From the Departement d'Hematologie, Institut Cochin, l'Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U567, Centre National de la Recherche Scientifique Unite\u0301 Mixtes de Recherche (CNRS UMR) 8104, Universite Rene-Descartes, Paris, France; INSERM U517, Faculte de Medecine, Dijon, France; and the Hopital Cochin, Assistance Publique-Ho\u0302pitaux de Paris (AP-HP), Service d'Hematologie, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Garrido","sequence":"additional","affiliation":[{"name":"From the Departement d'Hematologie, Institut Cochin, l'Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U567, Centre National de la Recherche Scientifique Unite\u0301 Mixtes de Recherche (CNRS UMR) 8104, Universite Rene-Descartes, Paris, France; INSERM U517, Faculte de Medecine, Dijon, France; and the Hopital Cochin, Assistance Publique-Ho\u0302pitaux de Paris (AP-HP), Service d'Hematologie, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stany","family":"Chre\u0301tien","sequence":"additional","affiliation":[{"name":"From the Departement d'Hematologie, Institut Cochin, l'Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U567, Centre National de la Recherche Scientifique Unite\u0301 Mixtes de Recherche (CNRS UMR) 8104, Universite Rene-Descartes, Paris, France; INSERM U517, Faculte de Medecine, Dijon, France; and the Hopital Cochin, Assistance Publique-Ho\u0302pitaux de Paris (AP-HP), Service d'Hematologie, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc\u0327ois","family":"Dreyfus","sequence":"additional","affiliation":[{"name":"From the Departement d'Hematologie, Institut Cochin, l'Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U567, Centre National de la Recherche Scientifique Unite\u0301 Mixtes de Recherche (CNRS UMR) 8104, Universite Rene-Descartes, Paris, France; INSERM U517, Faculte de Medecine, Dijon, France; and the Hopital Cochin, Assistance Publique-Ho\u0302pitaux de Paris (AP-HP), Service d'Hematologie, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Lacombe","sequence":"additional","affiliation":[{"name":"From the Departement d'Hematologie, Institut Cochin, l'Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U567, Centre National de la Recherche Scientifique Unite\u0301 Mixtes de Recherche (CNRS UMR) 8104, Universite Rene-Descartes, Paris, France; INSERM U517, Faculte de Medecine, Dijon, France; and the Hopital Cochin, Assistance Publique-Ho\u0302pitaux de Paris (AP-HP), Service d'Hematologie, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Mayeux","sequence":"additional","affiliation":[{"name":"From the Departement d'Hematologie, Institut Cochin, l'Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U567, Centre National de la Recherche Scientifique Unite\u0301 Mixtes de Recherche (CNRS UMR) 8104, Universite Rene-Descartes, Paris, France; INSERM U517, Faculte de Medecine, Dijon, France; and the Hopital Cochin, Assistance Publique-Ho\u0302pitaux de Paris (AP-HP), Service d'Hematologie, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michae\u0308la","family":"Fontenay","sequence":"additional","affiliation":[{"name":"From the Departement d'Hematologie, Institut Cochin, l'Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U567, Centre National de la Recherche Scientifique Unite\u0301 Mixtes de Recherche (CNRS UMR) 8104, Universite Rene-Descartes, Paris, France; INSERM U517, Faculte de Medecine, Dijon, France; and the Hopital Cochin, Assistance Publique-Ho\u0302pitaux de Paris (AP-HP), Service d'Hematologie, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021218160011900_REF1","doi-asserted-by":"crossref","unstructured":"Steensma DP, Tefferi A. 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