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<p>Genetic analyses have been included in scoring systems to improve the prognostic stratification of hematologic malignancies. Until now, molecular risk scores have not been included into the practical management of patients with polycythemia vera (PV). In this work, we studied 439 PV patients recruited from 15 French centers and described their mutational landscape using high-throughput sequencing. We detected an additional mutation in 53.3% of patients, 22.7% of them having 2 or more mutations. A Bayesian approach identified preferential associations between mutations. Based on these associations, we identified high molecular risk abnormalities in PV (PV-HMR), consisting in mutations in <i>SRSF2</i>, <i>IDH1/2</i>, <i>EZH2</i> or <i>NFE2</i> genes, copy number variations (CNV) and carrying 2 or more non-driver mutations. These PV-HMR were associated with decreased overall survival (OS) and/or transformation-free survival (TFS). Notably, <i>ASXL1</i> mutations were not associated with a pejorative impact on OS or TFS when isolated. Based on these results, we developed a genomic 3-tier classification that efficiently predicted OS and more importantly TFS independently of age, sex, history of thrombosis and leukocyte and platelet counts. This model outperformed the IWG-PV and MIPSS-PV scoring systems in predicting the hematologic evolution of PV patients, which was confirmed in 2 external cohorts.</p><p></p>

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A molecular signature predicts hematologic evolution in polycythemia vera patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月18日

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  • Olivier Mansier,
  • Eric Lippert,
  • Lina Benajiba,
  • Dana Ranta,
  • François Girodon,
  • Jean-Christophe Ianotto,
  • Aurélie Chauveau,
  • Lydia Roy,
  • Françoise Boyer,
  • Clémence Médiavilla,
  • Suzanne Tavitian,
  • Marion Divoux,
  • Mélinda Fanet,
  • Ivan Sloma,
  • Véronique De Mas,
  • Guillaume Denis,
  • Christopher Nunes Gomes,
  • Claire Calmettes,
  • Fiorenza Barraco,
  • Sarah Huet,
  • Fabienne Vacheret,
  • Mélanie Mercier,
  • Anne Parry,
  • Laurence Legros,
  • Juliette Soret-Dulphy,
  • Joris Argentin,
  • Léa Sureau,
  • Emmanuelle Verger,
  • Corentin Orvain,
  • Jérémie Riou,
  • Jean-Jacques Kiladjian,
  • Bruno Cassinat,
  • Valérie Ugo,
  • Damien Luque Paz,
  • Véronique De Mas

摘要

Genetic analyses have been included in scoring systems to improve the prognostic stratification of hematologic malignancies. Until now, molecular risk scores have not been included into the practical management of patients with polycythemia vera (PV). In this work, we studied 439 PV patients recruited from 15 French centers and described their mutational landscape using high-throughput sequencing. We detected an additional mutation in 53.3% of patients, 22.7% of them having 2 or more mutations. A Bayesian approach identified preferential associations between mutations. Based on these associations, we identified high molecular risk abnormalities in PV (PV-HMR), consisting in mutations in SRSF2, IDH1/2, EZH2 or NFE2 genes, copy number variations (CNV) and carrying 2 or more non-driver mutations. These PV-HMR were associated with decreased overall survival (OS) and/or transformation-free survival (TFS). Notably, ASXL1 mutations were not associated with a pejorative impact on OS or TFS when isolated. Based on these results, we developed a genomic 3-tier classification that efficiently predicted OS and more importantly TFS independently of age, sex, history of thrombosis and leukocyte and platelet counts. This model outperformed the IWG-PV and MIPSS-PV scoring systems in predicting the hematologic evolution of PV patients, which was confirmed in 2 external cohorts.