Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies

Joseph Saliba; Cécile Saint-Martin; Antonio Di Stefano; Gaëlle Lenglet; Caroline Marty; Boris Keren; Florence Pasquier; Véronique Della Valle; Lise Secardin; Gwendoline Leroy; Emna Mahfoudhi; Sarah Grosjean; Nathalie Droin; M'boyba Diop; Philippe Dessen; Sabine Charrier; Alberta Palazzo; Jane Merlevede; Jea ɤme Meniane; Christine Delaunay-Darivon; Pascal Fuseau; Françoise Isnard; Nicole Casadevall; Eric Solary; Najet Debili; Olivier A Bernard; Hana Raslova; Albert Najman; William Vainchenker; Christine Bellanné-Chantelot; Isabelle Plo

doi:10.1038/ng.3380

Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies

Joseph Saliba, Cécile Saint-Martin, Antonio Di Stefano, Gaëlle Lenglet, Caroline Marty, Boris Keren, Florence Pasquier, Véronique Della Valle, Lise Secardin, Gwendoline Leroy, Emna Mahfoudhi, Sarah Grosjean, Nathalie Droin, M'boyba Diop, Philippe Dessen, Sabine Charrier, Alberta Palazzo, Jane Merlevede, Jea ɤme Meniane, Christine Delaunay-DarivonPascal Fuseau, Françoise Isnard, Nicole Casadevall, Eric Solary, Najet Debili, Olivier A Bernard, Hana Raslova, Albert Najman, William Vainchenker, Christine Bellanné-Chantelot, Isabelle Plo

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Résumé

No major predisposition gene for familial myeloproliferative neoplasms (MPN) has been identified. Here we demonstrate that the autosomal dominant transmission of a 700-kb duplication in four genetically related families predisposes to myeloid malignancies, including MPN, frequently progressing to leukemia. Using induced pluripotent stem cells and primary cells, we demonstrate that overexpression of ATG2B and GSKIP enhances hematopoietic progenitor differentiation, including of megakaryocytes, by increasing progenitor sensitivity to thrombopoietin (TPO). ATG2B and GSKIP cooperate with acquired JAK2, MPL and CALR mutations during MPN development. Thus, the germline duplication may change the fitness of cells harboring signaling pathway mutations and increases the probability of disease development.

langue originale	Anglais
Pages (de - à)	1131-1140
Nombre de pages	10
journal	Nature Genetics
Volume	47
Numéro de publication	10
Les DOIs	https://doi.org/10.1038/ng.3380
état	Publié - 29 sept. 2015

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10.1038/ng.3380

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Saliba, J., Saint-Martin, C., Di Stefano, A., Lenglet, G., Marty, C., Keren, B., Pasquier, F., Della Valle, V., Secardin, L., Leroy, G., Mahfoudhi, E., Grosjean, S., Droin, N., Diop, M., Dessen, P., Charrier, S., Palazzo, A., Merlevede, J., Meniane, J. ., ... Plo, I. (2015). Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies. Nature Genetics, 47(10), 1131-1140. https://doi.org/10.1038/ng.3380

@article{78cd4c6e7f0a4aa2945a7f77174041d7,

title = "Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies",

abstract = "No major predisposition gene for familial myeloproliferative neoplasms (MPN) has been identified. Here we demonstrate that the autosomal dominant transmission of a 700-kb duplication in four genetically related families predisposes to myeloid malignancies, including MPN, frequently progressing to leukemia. Using induced pluripotent stem cells and primary cells, we demonstrate that overexpression of ATG2B and GSKIP enhances hematopoietic progenitor differentiation, including of megakaryocytes, by increasing progenitor sensitivity to thrombopoietin (TPO). ATG2B and GSKIP cooperate with acquired JAK2, MPL and CALR mutations during MPN development. Thus, the germline duplication may change the fitness of cells harboring signaling pathway mutations and increases the probability of disease development.",

author = "Joseph Saliba and C{\'e}cile Saint-Martin and {Di Stefano}, Antonio and Ga{\"e}lle Lenglet and Caroline Marty and Boris Keren and Florence Pasquier and {Della Valle}, V{\'e}ronique and Lise Secardin and Gwendoline Leroy and Emna Mahfoudhi and Sarah Grosjean and Nathalie Droin and M'boyba Diop and Philippe Dessen and Sabine Charrier and Alberta Palazzo and Jane Merlevede and Meniane, {Jea ɤme} and Christine Delaunay-Darivon and Pascal Fuseau and Fran{\c c}oise Isnard and Nicole Casadevall and Eric Solary and Najet Debili and {A Bernard}, Olivier and Hana Raslova and Albert Najman and William Vainchenker and Christine Bellann{\'e}-Chantelot and Isabelle Plo",

note = "Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

year = "2015",

month = sep,

day = "29",

doi = "10.1038/ng.3380",

language = "English",

volume = "47",

pages = "1131--1140",

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Saliba, J, Saint-Martin, C, Di Stefano, A, Lenglet, G, Marty, C, Keren, B, Pasquier, F, Della Valle, V, Secardin, L, Leroy, G, Mahfoudhi, E, Grosjean, S, Droin, N, Diop, M, Dessen, P, Charrier, S, Palazzo, A, Merlevede, J, Meniane, J, Delaunay-Darivon, C, Fuseau, P, Isnard, F, Casadevall, N, Solary, E, Debili, N, A Bernard, O, Raslova, H, Najman, A, Vainchenker, W, Bellanné-Chantelot, C & Plo, I 2015, 'Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies', Nature Genetics, VOL. 47, Numéro 10, p. 1131-1140. https://doi.org/10.1038/ng.3380

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T1 - Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies

AU - Saliba, Joseph

AU - Saint-Martin, Cécile

AU - Di Stefano, Antonio

AU - Lenglet, Gaëlle

AU - Marty, Caroline

AU - Keren, Boris

AU - Pasquier, Florence

AU - Della Valle, Véronique

AU - Secardin, Lise

AU - Leroy, Gwendoline

AU - Mahfoudhi, Emna

AU - Grosjean, Sarah

AU - Droin, Nathalie

AU - Diop, M'boyba

AU - Dessen, Philippe

AU - Charrier, Sabine

AU - Palazzo, Alberta

AU - Merlevede, Jane

AU - Meniane, Jea ɤme

AU - Delaunay-Darivon, Christine

AU - Fuseau, Pascal

AU - Isnard, Françoise

AU - Casadevall, Nicole

AU - Solary, Eric

AU - Debili, Najet

AU - A Bernard, Olivier

AU - Raslova, Hana

AU - Najman, Albert

AU - Vainchenker, William

AU - Bellanné-Chantelot, Christine

AU - Plo, Isabelle

PY - 2015/9/29

Y1 - 2015/9/29

N2 - No major predisposition gene for familial myeloproliferative neoplasms (MPN) has been identified. Here we demonstrate that the autosomal dominant transmission of a 700-kb duplication in four genetically related families predisposes to myeloid malignancies, including MPN, frequently progressing to leukemia. Using induced pluripotent stem cells and primary cells, we demonstrate that overexpression of ATG2B and GSKIP enhances hematopoietic progenitor differentiation, including of megakaryocytes, by increasing progenitor sensitivity to thrombopoietin (TPO). ATG2B and GSKIP cooperate with acquired JAK2, MPL and CALR mutations during MPN development. Thus, the germline duplication may change the fitness of cells harboring signaling pathway mutations and increases the probability of disease development.

AB - No major predisposition gene for familial myeloproliferative neoplasms (MPN) has been identified. Here we demonstrate that the autosomal dominant transmission of a 700-kb duplication in four genetically related families predisposes to myeloid malignancies, including MPN, frequently progressing to leukemia. Using induced pluripotent stem cells and primary cells, we demonstrate that overexpression of ATG2B and GSKIP enhances hematopoietic progenitor differentiation, including of megakaryocytes, by increasing progenitor sensitivity to thrombopoietin (TPO). ATG2B and GSKIP cooperate with acquired JAK2, MPL and CALR mutations during MPN development. Thus, the germline duplication may change the fitness of cells harboring signaling pathway mutations and increases the probability of disease development.

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JF - Nature Genetics

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