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3. Cohorte RADICO-ILD2 (Projet FIFA) : atteintes asymptomatiques chez les apparentés de porteurs de variants de gènes liés aux télomères

Author

Guerin, C., primary, Kannengiesser, C., additional, Bramki, K., additional, Jouneau, S., additional, Prevot, G., additional, Marchand-Adam, S., additional, Dominique, S., additional, Andréjak, C., additional, Wemeau, L., additional, Crestani, B., additional, Lainey, E., additional, Sicre De Fontbrune, F., additional, Plessier, A., additional, Dubus, J.C., additional, Clement, A., additional, Nunes, H., additional, Valeyre, D., additional, Nathan, N., additional, Cadranel, J., additional, Israel Biet, D., additional, Reynaud-Gaubert, M., additional, Bonniaud, P., additional, Dufaure-Gare, I., additional, Plouvier, L., additional, Nasri, I., additional, Lassus, A., additional, Ba, I., additional, Cottin, V., additional, Gueguen, S., additional, and Borie, R., additional

Published
2024
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5. Thrombopénie immunologique après allogreffe de cellules souches hématopoïétiques : résultats d’une étude rétrospective observationnelle multicentrique portant sur 35 patients

Author

Gondé, A., primary, Legal, A., additional, Sicre De Fontbrune, F., additional, Puyade, M., additional, D’aveni, M., additional, Béguin, Y., additional, Botella Garcia, C., additional, Brissot, E., additional, Daguindau, E., additional, Godeau, B., additional, Michel, M., additional, and Comont, T., additional

Published
2023
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7. L’inhibiteur oral du facteur b du complément iptacopan chez les patients (pts) atteints d’hémoglobinurie paroxystique nocturne (hpn) avec hémolyse active malgré un traitement anti-c5 : efficacité et sécurité à long terme après arrêt d’éculizumab (ecu)

Author

Peffault De Latour, R., primary, Roth, A., additional, Soret, J., additional, Frieri, C., additional, Sicre De Fontbrune, F., additional, Marano, L., additional, Alashkar, F., additional, Benajiba, L., additional, Marotta, S., additional, Kulmatycki, K., additional, Nidamarthy, P.K., additional, Fagan, N., additional, Junge, G., additional, and Risitano, A., additional

Published
2022
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8. S162: SOMATIC GENETIC LANDSCAPE IN GATA2 DEFICIENCY PATIENTS

Author

Largeaud, L., primary, Collin, M., additional, Monselet, N., additional, Vergez, F., additional, Larcher, L., additional, Hirsch, P., additional, Duployez, N., additional, Bustamante, J., additional, Bellanné-Chantelot, C., additional, Donadieu, J., additional, Sicre de Fontbrune, F., additional, Nolla, M., additional, Fieschi, C., additional, Delhommeau, F., additional, Delabesse, E., additional, and Pasquet, M., additional

Published
2022
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9. P813: EFFICACY, TREATMENT ADMINISTRATION SATISFACTION AND SAFETY OF SUBCUTANEOUS RAVULIZUMAB THROUGH 1 YEAR IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WHO RECEIVED PRIOR INTRAVENOUS ECULIZUMAB

Author

Yenerel, M. N., primary, Sicre de Fontbrune, F., additional, Piatek, C., additional, Sahin, F., additional, Füreder, W., additional, Ogawa, M., additional, Tomazos, I., additional, Doll, H., additional, Ozol-Godfrey, A., additional, Sierra, J. R., additional, and Szer, J., additional

Published
2022
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13. Einsatz des oralen Komplementfaktor B-Inhibitors Iptacopan bei Patienten (pts) mit Paroxysmaler Nächtlicher Hämoglobinurie (PNH) mit anhaltende Hämolyse trotz einer Anti-C5 Therapie : langfristige Wirksamkeit und Sicherheit nach dem Absetzen von Eculizumab (ECU)

Author

Röth, Alexander, Peffault de Latour, R., Soret, J., Frieri, C., Sicre de Fontbrune, F., Marano, L., Alashkar, Ferras, Benajiba, L., Marotta, S., Kulmatycki, K., Nidamarthy, P. K., Fagan, N., Junge, G., and Risitano, A. M.

Subjects
Medizin
Published
2022

14. Suivi de l’utilisation de l’Eltrombopag en vie réelle en France à partir des données de l’Observatoire National de l’Insuffisance Médullaire (RIME) : étude REVEPI

Author

Sicre De Fontbrune, F., primary, Barraco, F., additional, Dalle, J.H., additional, Forcade, E., additional, Terriou, L., additional, Berceanu, A., additional, Lebon, D., additional, Thépot, S., additional, Abraham, J., additional, Fahd, M., additional, Lioure, B., additional, Contejean, A., additional, Moluçon Chabrot, C., additional, Leblanc, T., additional, Leclerc-Teffahi, S., additional, Affinito, S., additional, Kamar, D., additional, Havet, A., additional, Bénard, S., additional, and Regis, P.L., additional

Published
2021
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15. Téloméropathies de recrutement hématologique : étude de 15 cas

Author

Antoine, P., primary, Terriou, L., additional, Lefèvre, G., additional, Kannengiesser, C., additional, Sanges, S., additional, Launay, D., additional, Sobanski, V., additional, Hachulla, É., additional, Louvet, A., additional, Willemin, M.-C., additional, Renaut-Marceau, A., additional, Lainey, E., additional, Sicre de Fontbrune, F., additional, and Farhat, M.-M., additional

Published
2021
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18. The Oral Complement Factor B Inhibitor Iptacopan is Safe and Effective in Improving Hematological Response in Paroxysmal Nocturnal Hemoglobinuria Patients with Poor Response to Eculizumab, even in Monotherapy

Author

Risitano, A.M., Röth, Alexander, Soret, J., Frieri, C., Sicre de Fontbrune, F., Marano, L., Alashkar, Ferras, Benajiba, L., Marotta, S., Rozenberg, I., Milojevic, J., End, P., Nidamarthy, P.K., Junge, G., and Peffault de Latour, R.

Subjects
Medizin
Abstract

Kein CA

Published
2021

20. L’étude transcriptomique par mRNA sequencing des lésions cutanées de GVH chronique à type de lichen plan et de morphée identifie TREM1 comme cible thérapeutique dans le lichen plan

Author

Zouali, H., primary, Lemasson, J., additional, Calugareanu, A., additional, Battail, C., additional, Michonneau, D., additional, Le Buanec, H., additional, Cassius, C., additional, Robin, M., additional, Sicre de Fontbrune, F., additional, Peffault de La Tour, R., additional, Jachiet, M., additional, Bagot, M., additional, Socié, G., additional, Deleuze, J.-F., additional, and Bouaziz, J.-D., additional

Published
2020
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21. FLAG-sequential regimen followed by bone marrow transplantation for myelodysplastic syndrome or acute leukemia in patients with Fanconi anemia: a Franco-Brazilian study

Author

Debureaux, P. E., primary, Sicre de Fontbrune, F., additional, Bonfim, C., additional, Dalle, J. H., additional, Buchbinder, N., additional, Bertrand, Y., additional, Renard, C., additional, Forcade, E., additional, Fernandes, J., additional, Talbot, A., additional, Pasquini, R., additional, Soulier, J., additional, Leblanc, T., additional, Socie, G., additional, and Peffault de Latour, R., additional

Published
2020
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24. Étude transcriptomique par mRNA sequencing des lésions cutanées de GVH chronique à type de lichen plan et de morphée chez le patient allogreffé

Author

Lemasson, J., primary, Zouali, H., additional, Le Buanec, H., additional, Michonneau, D., additional, Boland, A., additional, Fin, B., additional, Amode, R., additional, Battail, C., additional, Bagot, M., additional, De Masson, A., additional, Robin, M., additional, Sicre de Fontbrune, F., additional, Bensussan, A., additional, Deleuze, J.-F., additional, Socié, G., additional, and Bouaziz, J.-D., additional

Published
2019
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25. S863 ONE-YEAR EFFICACY OF RAVULIZUMAB (ALXN1210) IN ADULT PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA NAIVE TO COMPLEMENT INHIBITORS

Author

Schrezenmeier, H., primary, Kulasekararaj, A., additional, Mitchell, L., additional, Sicre de Fontbrune, F., additional, Devo, T., additional, Okamoto, S., additional, Wells, R., additional, Rottinghaus, S., additional, Liu, P., additional, Ortiz, S., additional, Shafner, L., additional, Lee, J.W., additional, and Socie, G., additional

Published
2019
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27. Results from a Phase 3, Multicenter, Noninferiority Study of Ravulizumab (ALXN1210) versus Eculizumab (ECU) in Adult Patients (pts) with Paroxysmal Nocturnal Hemoglubinuria (PNH) Naive to Complement Inhibitors (CI)

Author

Schrezenmeier, H., additional, Lee, J.W., additional, Rottinghaus, S.T., additional, Lee, L.W., additional, Pessoa, V., additional, Gualandro, S., additional, Füreder, W., additional, Ptushkin, V., additional, Sicre de Fontbrune, F., additional, Volles, L., additional, Shafner, L., additional, Damokosh, A., additional, Aguzzi, R., additional, Pradhan, R., additional, Ortis, S., additional, and Hill, A., additional

Published
2019
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31. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells

Author

Mathew, N.R., Baumgartner, F., Braun, L., O'Sullivan, D., Thomas, S., Waterhouse, M., Muller, T.A., Hanke, K., Taromi, S., Apostolova, P., Illert, A.L., Melchinger, W., Duquesne, S., Schmitt-Graeff, A., Osswald, L., Yan, K.L., Weber, A, Tugues, S., Spath, S., Pfeifer, D., Follo, M., Claus, R., Lubbert, M., Rummelt, C., Bertz, H., Wasch, R., Haag, J., Schmidts, A., Schultheiss, M., Bettinger, D., Thimme, R., Ullrich, E., Tanriver, Y., Vuong, G.L., Arnold, R., Hemmati, P., Wolf, D., Ditschkowski, M., Jilg, C., Wilhelm, K., Leiber, C., Gerull, S., Halter, J., Lengerke, C., Pabst, T., Schroeder, T., Kobbe, G., Rosler, W., Doostkam, S., Meckel, S., Stabla, K., Metzelder, S.K., Halbach, S., Brummer, T., Hu, Z, Dengjel, J., Hackanson, B., Schmid, C., Holtick, U., Scheid, C., Spyridonidis, A., Stolzel, F., Ordemann, R., Muller, L.P., Sicre-de-Fontbrune, F., Ihorst, G., Kuball, J., Ehlert, J.E., Feger, D., Wagner, E.M., Cahn, J.Y., Schnell, J., Kuchenbauer, F., Bunjes, D., Chakraverty, R., Richardson, S., Gill, S., Kroger, N., Ayuk, F., Vago, L., Ciceri, F., Muller, A.M., Kondo, T., Teshima, T., Klaeger, S., Kuster, B., Kim, D.D.H., Weisdorf, D., Velden, W.J. van der, Dorfel, D., Bethge, W., Hilgendorf, I., Hochhaus, A., Andrieux, G., Borries, M., Busch, H., Magenau, J., Reddy, P., Labopin, M., Antin, J.H., et al., Mathew, N.R., Baumgartner, F., Braun, L., O'Sullivan, D., Thomas, S., Waterhouse, M., Muller, T.A., Hanke, K., Taromi, S., Apostolova, P., Illert, A.L., Melchinger, W., Duquesne, S., Schmitt-Graeff, A., Osswald, L., Yan, K.L., Weber, A, Tugues, S., Spath, S., Pfeifer, D., Follo, M., Claus, R., Lubbert, M., Rummelt, C., Bertz, H., Wasch, R., Haag, J., Schmidts, A., Schultheiss, M., Bettinger, D., Thimme, R., Ullrich, E., Tanriver, Y., Vuong, G.L., Arnold, R., Hemmati, P., Wolf, D., Ditschkowski, M., Jilg, C., Wilhelm, K., Leiber, C., Gerull, S., Halter, J., Lengerke, C., Pabst, T., Schroeder, T., Kobbe, G., Rosler, W., Doostkam, S., Meckel, S., Stabla, K., Metzelder, S.K., Halbach, S., Brummer, T., Hu, Z, Dengjel, J., Hackanson, B., Schmid, C., Holtick, U., Scheid, C., Spyridonidis, A., Stolzel, F., Ordemann, R., Muller, L.P., Sicre-de-Fontbrune, F., Ihorst, G., Kuball, J., Ehlert, J.E., Feger, D., Wagner, E.M., Cahn, J.Y., Schnell, J., Kuchenbauer, F., Bunjes, D., Chakraverty, R., Richardson, S., Gill, S., Kroger, N., Ayuk, F., Vago, L., Ciceri, F., Muller, A.M., Kondo, T., Teshima, T., Klaeger, S., Kuster, B., Kim, D.D.H., Weisdorf, D., Velden, W.J. van der, Dorfel, D., Bethge, W., Hilgendorf, I., Hochhaus, A., Andrieux, G., Borries, M., Busch, H., Magenau, J., Reddy, P., Labopin, M., and Antin, J.H., et al.

Abstract

Contains fulltext : 190745.pdf (publisher's version ) (Closed access), Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD(+) leukemia cells. This synergized with the allogeneic CD8(+) T cell response, leading to long-term survival in six mouse models of FLT3-ITD(+) AML. Sorafenib-related IL-15 production caused an increase in CD8(+)CD107a(+)IFN-gamma(+) T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD(+) AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8(+) T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.

Published
2018

32. Le screening systématique de l’antigène galactomannane sérique (GM) chez les patients asymptomatiques allogreffés de moelle sous prophylaxie efficace par posaconazole ou voriconazole devrait être remplacé par un screening ciblé chez les patients symptomatiques

Author

Denis, B., primary, Moatti, H., additional, Sicre de Fontbrune, F., additional, Resche-Rigon, M., additional, Boissel, N., additional, Touratier, S., additional, Peffault de la Tour, R., additional, Guigue, N., additional, Bretagne, S., additional, and Molina, J.M., additional

Published
2018
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33. Cutaneous presentation of adult T-cell leukemia/lymphoma (ATLL). Single-center study on 37 patients in metropolitan France between 1996 and 2016

Author

Hurabielle, C., primary, Battistella, M., additional, Ram-Wolff, C., additional, Fite, C., additional, Meignin, V., additional, Rivet, J., additional, Vignon-Pennamen, M.-D., additional, de Risi-Pugliese, T., additional, Raffoux, E., additional, Arnulf, B., additional, Oksenhendler, E., additional, Sicre de Fontbrune, F., additional, Peffault de Latour, R., additional, Socié, G., additional, Bouaziz, J.-D., additional, Lebbé, C., additional, Bensussan, A., additional, and Bagot, M., additional

Published
2018
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34. KIR3DL2 expression in patients with adult T-cell lymphoma/leukaemia

Author

Hurabielle, C., primary, Leboeuf, C., additional, Ram-Wolff, C., additional, Meignin, V., additional, Rivet, J., additional, Vignon-Pennamen, M.-D., additional, Bonnafous, C., additional, Sicard, H., additional, Fite, C., additional, Raffoux, E., additional, Arnulf, B., additional, Oksenhendler, E., additional, Sicre de Fontbrune, F., additional, Peffault de Latour, R., additional, Socié, G., additional, Bouaziz, J.-D., additional, Lebbé, C., additional, Bensussan, A., additional, Janin, A., additional, Bagot, M., additional, and Battistella, M., additional

Published
2018
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35. Syndrome dermato-pulmonaire avec anticorps anti-MDA5 après allogreffe de cellules souches hématopoïétiques

Author

Lepelletier, C., primary, Bengoufa, D., additional, Lyes, Z., additional, de Masson, A., additional, Chasset, F., additional, Jachiet, M., additional, Michonneau, D., additional, Robin, M., additional, Peffault-de-Latour, R., additional, Sicre-de-Fontbrune, F., additional, Tandjaoui-Lambiotte, Y., additional, Bensussan, A., additional, Rybojad, M., additional, Tazi, A., additional, Bagot, M., additional, Socié, G., additional, Bergeron, A., additional, and Bouaziz, J.-D., additional

Published
2016
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37. High response rates in patients treated with ruxolitinib for corticosteroid-refractory Graft-versus-host disease: analysis including 13 Transplant Centers

Author

Zeiser, R., Lengerke, C., Spoerl, S., Maas-Bauer, K., Ditschkowski, M., Ecsedi, M., Sockel, K., Ayuk, F., Sicre-de-Fontbrune, F., Na, I-K, Ajib, S., Verbeek, M., Nogai, H., Holtick, U., Wolf, D., Schuler, E., Meyer, E., Apostolova, P., Illert, L., Bertz, H., Marks, R., Waesch, R., Hackanson, B., Scheid, C., Ordemann, R., Bug, G., Kobbe, G., Negrin, R., Arnold, R., Kroeger, N., Passweg, J., Halter, J., Socie, G., Beelen, D., Finke, J., Peschel, C., Duyster, J., von Bubnoff, N., Zeiser, R., Lengerke, C., Spoerl, S., Maas-Bauer, K., Ditschkowski, M., Ecsedi, M., Sockel, K., Ayuk, F., Sicre-de-Fontbrune, F., Na, I-K, Ajib, S., Verbeek, M., Nogai, H., Holtick, U., Wolf, D., Schuler, E., Meyer, E., Apostolova, P., Illert, L., Bertz, H., Marks, R., Waesch, R., Hackanson, B., Scheid, C., Ordemann, R., Bug, G., Kobbe, G., Negrin, R., Arnold, R., Kroeger, N., Passweg, J., Halter, J., Socie, G., Beelen, D., Finke, J., Peschel, C., Duyster, J., and von Bubnoff, N.

Published
2015

38. Présence de populations lymphocytaires Th1, Th17 et Tc17 dans la réaction du greffon contre l’hôte chronique (GVHc) psoriasiforme

Author

Chasset, F., primary, Le-Buanec, H., additional, Sicre de Fontbrune, F., additional, De Masson, A., additional, Rivet, J., additional, Bergeron, A., additional, Frumholtz, L., additional, Robin, M., additional, Rybojad, M., additional, Roux, J., additional, Tazi, A., additional, Peffault de La Tour, R., additional, Bagot, M., additional, Socié, G., additional, Bensussan, A., additional, and Bouaziz, J.-D., additional

Published
2015
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41. Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity

Author

Jachiet, M., primary, de Masson, A., additional, Peffault de Latour, R., additional, Rybojad, M., additional, Robin, M., additional, Bourhis, J.-H., additional, Xhaard, A., additional, Dhedin, N., additional, Sicre de Fontbrune, F., additional, Suarez, F., additional, Barete, S., additional, Parquet, N., additional, Nguyen, S., additional, Ades, L., additional, Rubio, M.-T., additional, Wittnebel, S., additional, Bagot, M., additional, Socié, G., additional, and Bouaziz, J.-D., additional

Published
2014
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42. GVH cutanées chroniques ulcérées : spectre clinique et évolutif sur une cohorte rétrospective de 25 patients

Author

Jachiet, M., primary, de Masson, A., additional, Latour, R. Peffault de, additional, Bourhis, J.-H., additional, Robin, M., additional, Rybojad, M., additional, Xhaard, A., additional, Sicre de Fontbrune, F., additional, Suarez, F., additional, Barete, S., additional, Wittnebel, S., additional, Bagot, M., additional, Socié, G., additional, and Bouaziz, J.D., additional

Published
2013
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44. KIR3DL2 expression in patients with adult T-cell lymphoma/leukaemia.

Author

Hurabielle, C., Leboeuf, C., Ram-Wolff, C., Meignin, V., Rivet, J., Vignon-Pennamen, M.-D., Bonnafous, C., Sicard, H., Fite, C., Raffoux, E., Arnulf, B., Oksenhendler, E., Sicre de Fontbrune, F., Peffault de Latour, R., Socié, G., Bouaziz, J.-D., Lebbé, C., Bensussan, A., Janin, A., and Bagot, M.

Subjects
KILLER cells, T-cell lymphoma, LEUKEMIA, PATIENTS
Published
2018
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48. Haematological features of telomere biology disorders diagnosed in adulthood: A French nationwide study of 127 patients.

Author

Maillet F, Galimard JE, Borie R, Lainey E, Larcher L, Passet M, Plessier A, Leblanc T, Terriou L, Lebon D, Alcazer V, Cathebras P, Loschi M, Wadih AC, Marcais A, Marceau-Renaut A, Couque N, Lioure B, Soulier J, Ba I, Socié G, Peffault de Latour R, Kannengiesser C, and Sicre de Fontbrune F

Subjects
Humans, Male, Female, Adult, Middle Aged, France epidemiology, Adolescent, Young Adult, Aged, Telomere genetics, Prognosis, Mutation, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute diagnosis, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes mortality
Abstract

Data on haematological features of telomere biology disorders (TBD) remain scarce. We describe haematological, extra-haematological characteristics and prognosis of 127 genetically confirmed TBD patients diagnosed after the age of 15. Ninety-three index cases and 34 affected relatives were included. At diagnosis of TBD, 76.3% of index cases had haematological features, half pulmonary features and a third liver features. At diagnosis, bone marrow failure (BMF) was present in 59 (46.5%), myelodysplastic syndrome (MDS) in 22 (17.3%) and acute myeloid leukaemia (AML) in 2 (1.6%) while 13 (10.2%) developed or worsened bone marrow involvement during follow-up. At diagnosis, compared to MDS/AML patients, BMF patients were younger (median 23.1 years vs. 43.8, p = 0.007), and had a better outcome (4-year overall survival 76.3% vs. 31.8%, p < 0.001). While frequencies and burden of cytogenetical and somatic mutations increased significantly in myeloid malignancies, some abnormalities were also observed in patients with normal blood counts and BMF, notably somatic spliceosome variants. Solid cancers developed in 8.7% patients, mainly human papillomavirus-related cancers and hepatocellular carcinomas. TBD is a multiorgan progressive disease. While BMF is the main haematological disorder, high-risk myeloid malignancies are common, and are, together with age, the only factors associated with a worse outcome., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Published
2024
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49. Germ line ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predisposition.

Author

Zerella JR, Homan CC, Arts P, Lin X, Spinelli SJ, Venugopal P, Babic M, Brautigan PJ, Truong L, Arriola-Martinez L, Moore S, Hollins R, Parker WT, Nguyen H, Kassahn KS, Branford S, Feurstein S, Larcher L, Sicre de Fontbrune F, Demirdas S, de Munnik S, Antoine-Poirel H, Brichard B, Mansour S, Gordon K, Wlodarski MW, Koppayi A, Dobbins S, Mutsaers PGNJ, Nichols KE, Oak N, DeMille D, Mao R, Crawford A, McCarrier J, Basel D, Flores-Daboub J, Drazer MW, Phillips K, Poplawski NK, Birdsey GM, Pirri D, Ostergaard P, Simons A, Godley LA, Ross DM, Hiwase DK, Soulier J, Brown AL, Carmichael CL, Scott HS, and Hahn CN

Subjects
Humans, Male, Female, Adult, Animals, Genetic Predisposition to Disease, Hematologic Neoplasms genetics, Hematologic Neoplasms pathology, Mice, Thrombocytopenia genetics, Thrombocytopenia pathology, Mutation, Missense, Pedigree, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes pathology, Core Binding Factor Alpha 2 Subunit genetics, Middle Aged, Cytopenia, Transcriptional Regulator ERG genetics, Haploinsufficiency, Germ-Line Mutation
Abstract

Abstract: The genomics era has facilitated the discovery of new genes that predispose individuals to bone marrow failure (BMF) and hematological malignancy (HM). We report the discovery of ETS-related gene (ERG), a novel, autosomal dominant BMF/HM predisposition gene. ERG is a highly constrained transcription factor that is critical for definitive hematopoiesis, stem cell function, and platelet maintenance. ERG colocalizes with other transcription factors, including RUNX family transcription factor 1 (RUNX1) and GATA binding protein 2 (GATA2), on promoters or enhancers of genes that orchestrate hematopoiesis. We identified a rare heterozygous ERG missense variant in 3 individuals with thrombocytopenia from 1 family and 14 additional ERG variants in unrelated individuals with BMF/HM, including 2 de novo cases and 3 truncating variants. Phenotypes associated with pathogenic germ line ERG variants included cytopenias (thrombocytopenia, neutropenia, and pancytopenia) and HMs (acute myeloid leukemia, myelodysplastic syndrome, and acute lymphoblastic leukemia) with onset before 40 years. Twenty ERG variants (19 missense and 1 truncating), including 3 missense population variants, were functionally characterized. Thirteen potentially pathogenic erythroblast transformation specific (ETS) domain missense variants displayed loss-of-function (LOF) characteristics, thereby disrupting transcriptional transactivation, DNA binding, and/or nuclear localization. Selected variants overexpressed in mouse fetal liver cells failed to drive myeloid differentiation and cytokine-independent growth in culture and to promote acute erythroleukemia when transplanted into mice, concordant with these being LOF variants. Four individuals displayed somatic genetic rescue by copy neutral loss of heterozygosity. Identification of predisposing germ line ERG variants has clinical implications for patient and family diagnoses, counseling, surveillance, and treatment strategies, including selection of bone marrow donors and cell or gene therapy., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Published
2024
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50. Alemtuzumab-based conditioning regimen before hematopoietic stem cell transplantation in patients with short telomere syndromes: a retrospective study of the SFGM-TC.

Author

Hussein-Agha R, Kannengiesser C, Lainey E, Marcais A, Srour M, Sterin A, Buchbinder N, Borie R, Plessier A, Socié G, Peffault de Latour R, and Sicre de Fontbrune F

Subjects
Humans, Retrospective Studies, Adult, Male, Female, Middle Aged, Adolescent, Young Adult, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Vidarabine administration & dosage, Telomere Shortening, Alemtuzumab therapeutic use, Alemtuzumab pharmacology, Alemtuzumab administration & dosage, Transplantation Conditioning methods, Hematopoietic Stem Cell Transplantation methods
Abstract

While HSCT is the only curative option for patients with short telomere syndromes (STSs) and severe bone marrow failure (BMF) or myeloid malignancies (MM), their increase sensitivity to conditioning regimen strongly affect outcomes. To minimize HSCT related mortality, alemtuzumab-based conditioning regimens have been proposed, but the number of patients transplanted with those regimens reported in the literature remains very low. We retrospectively analyzed outcome of adults and adolescents with STSs transplanted after an alemtuzumab, fludarabine and cyclophosphamide based regimen registered by the SFGM-TC. Seven patients were transplanted for a BMF and 5 for a MM (median age 34 years, (IQR [22-45])). The 2-year GRFS for patients with MM was 20% (95% CI [3;100]), and 57% (95% CI [30;100]) in others. In univariate (hazard ratio, HR = 6, 95% CI [1;31]) and multivariate analysis (HR = 26, 95% CI [2;414]) stem cell source was a predictive factor for GRFS. Three of the 5 patients with pre-transplant MM relapsed and 2 of them died at last follow up. The 2-year OS was 66% (95% CI [43;99]) in the whole cohort with a median follow up of 32 months (IQR [13-56]). In conclusion, Alemtuzumab-based conditioning regimen with bone marrow is an option for patients with STSs and BMF, but others modalities have to be explored for patients with MM., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Published
2024
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