An inherited gain-of-function risk allele in EPOR predisposes to familial JAK2V617F myeloproliferative neoplasms

Graciela Rabadan Moraes; Florence Pasquier; Christophe Marzac; Eric Deconinck; Carlotta Caterina Damanti; Gwendoline Leroy; Mira El-Khoury; Wassim El Nemer; Jean Jacques Kiladjian; Hana Raslova; Albert Najman; William Vainchenker; Caroline Marty; Christine Bellanné-Chantelot; Isabelle Plo

doi:10.1111/bjh.18165

An inherited gain-of-function risk allele in EPOR predisposes to familial JAK2^V617F myeloproliferative neoplasms

Graciela Rabadan Moraes, Florence Pasquier, Christophe Marzac, Eric Deconinck, Carlotta Caterina Damanti, Gwendoline Leroy, Mira El-Khoury, Wassim El Nemer, Jean Jacques Kiladjian, Hana Raslova, Albert Najman, William Vainchenker, Caroline Marty, Christine Bellanné-Chantelot, Isabelle Plo

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Myeloproliferative neoplasms (MPN) are mainly sporadic but inherited variants have been associated with higher risk development. Here, we identified an EPOR variant (EPOR^P488S) in a large family diagnosed with JAK2^V617F-positive polycythaemia vera (PV) or essential thrombocytosis (ET). We investigated its functional impact on JAK2^V617F clonal amplification in patients and found that the variant allele fraction (VAF) was low in PV progenitors but increase strongly in mature cells. Moreover, we observed that EPOR^P488S alone induced a constitutive phosphorylation of STAT5 in cell lines or primary cells. Overall, this study points for searching inherited-risk alleles affecting the JAK2/STAT pathway in MPN.

Original language	English
Pages (from-to)	131-136
Number of pages	6
Journal	British Journal of Haematology
Volume	198
Issue number	1
DOIs	https://doi.org/10.1111/bjh.18165
Publication status	Published - 1 Jul 2022

Keywords

EPOR
JAK2
familial myeloproliferative neoplasms
germline factor
predisposition

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10.1111/bjh.18165

Cite this

Rabadan Moraes, G., Pasquier, F., Marzac, C., Deconinck, E., Damanti, C. C., Leroy, G., El-Khoury, M., El Nemer, W., Kiladjian, J. J., Raslova, H., Najman, A., Vainchenker, W., Marty, C., Bellanné-Chantelot, C., & Plo, I. (2022). An inherited gain-of-function risk allele in EPOR predisposes to familial JAK2^V617F myeloproliferative neoplasms. British Journal of Haematology, 198(1), 131-136. https://doi.org/10.1111/bjh.18165

@article{0390db5eb3a84adaa703873c08c0006f,

title = "An inherited gain-of-function risk allele in EPOR predisposes to familial JAK2V617F myeloproliferative neoplasms",

abstract = "Myeloproliferative neoplasms (MPN) are mainly sporadic but inherited variants have been associated with higher risk development. Here, we identified an EPOR variant (EPORP488S) in a large family diagnosed with JAK2V617F-positive polycythaemia vera (PV) or essential thrombocytosis (ET). We investigated its functional impact on JAK2V617F clonal amplification in patients and found that the variant allele fraction (VAF) was low in PV progenitors but increase strongly in mature cells. Moreover, we observed that EPORP488S alone induced a constitutive phosphorylation of STAT5 in cell lines or primary cells. Overall, this study points for searching inherited-risk alleles affecting the JAK2/STAT pathway in MPN.",

keywords = "EPOR, JAK2, familial myeloproliferative neoplasms, germline factor, predisposition",

author = "{Rabadan Moraes}, Graciela and Florence Pasquier and Christophe Marzac and Eric Deconinck and Damanti, {Carlotta Caterina} and Gwendoline Leroy and Mira El-Khoury and {El Nemer}, Wassim and Kiladjian, {Jean Jacques} and Hana Raslova and Albert Najman and William Vainchenker and Caroline Marty and Christine Bellann{\'e}-Chantelot and Isabelle Plo",

note = "Publisher Copyright: {\textcopyright} 2022 British Society for Haematology and John Wiley & Sons Ltd.",

year = "2022",

month = jul,

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doi = "10.1111/bjh.18165",

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Rabadan Moraes, G, Pasquier, F, Marzac, C, Deconinck, E, Damanti, CC, Leroy, G, El-Khoury, M, El Nemer, W, Kiladjian, JJ, Raslova, H, Najman, A, Vainchenker, W, Marty, C, Bellanné-Chantelot, C & Plo, I 2022, 'An inherited gain-of-function risk allele in EPOR predisposes to familial JAK2^V617F myeloproliferative neoplasms', British Journal of Haematology, vol. 198, no. 1, pp. 131-136. https://doi.org/10.1111/bjh.18165

TY - JOUR

T1 - An inherited gain-of-function risk allele in EPOR predisposes to familial JAK2V617F myeloproliferative neoplasms

AU - Rabadan Moraes, Graciela

AU - Pasquier, Florence

AU - Marzac, Christophe

AU - Deconinck, Eric

AU - Damanti, Carlotta Caterina

AU - Leroy, Gwendoline

AU - El-Khoury, Mira

AU - El Nemer, Wassim

AU - Kiladjian, Jean Jacques

AU - Raslova, Hana

AU - Najman, Albert

AU - Vainchenker, William

AU - Marty, Caroline

AU - Bellanné-Chantelot, Christine

AU - Plo, Isabelle

PY - 2022/7/1

Y1 - 2022/7/1

N2 - Myeloproliferative neoplasms (MPN) are mainly sporadic but inherited variants have been associated with higher risk development. Here, we identified an EPOR variant (EPORP488S) in a large family diagnosed with JAK2V617F-positive polycythaemia vera (PV) or essential thrombocytosis (ET). We investigated its functional impact on JAK2V617F clonal amplification in patients and found that the variant allele fraction (VAF) was low in PV progenitors but increase strongly in mature cells. Moreover, we observed that EPORP488S alone induced a constitutive phosphorylation of STAT5 in cell lines or primary cells. Overall, this study points for searching inherited-risk alleles affecting the JAK2/STAT pathway in MPN.

AB - Myeloproliferative neoplasms (MPN) are mainly sporadic but inherited variants have been associated with higher risk development. Here, we identified an EPOR variant (EPORP488S) in a large family diagnosed with JAK2V617F-positive polycythaemia vera (PV) or essential thrombocytosis (ET). We investigated its functional impact on JAK2V617F clonal amplification in patients and found that the variant allele fraction (VAF) was low in PV progenitors but increase strongly in mature cells. Moreover, we observed that EPORP488S alone induced a constitutive phosphorylation of STAT5 in cell lines or primary cells. Overall, this study points for searching inherited-risk alleles affecting the JAK2/STAT pathway in MPN.

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