Frequent and clinically relevant germline DNA repair gene variants in young and familial myeloproliferative neoplasms

Blood Cancer Journal 2026 Open access

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Authors: Robert Meyer, María Jimena Rodriguez, Madeline J. Caduc, Kim Kricheldorf, Matthias Begemann, Florian Kraft, Isabel Spier, Daniela Dey, Nergis Güzel, Kerstin Becker, Julian Baumeister, Marcelo AS de Toledo
+8 more Susanne Isfort, Ulrich Germing, Stefan Aretz, Tim H. Brümmendorf, Ingo Kurth, Miriam Elbracht, Lino L. Teichmann, Steffen Koschmieder
DOI: 10.1038/s41408-025-01433-3
Cited by: 2
References: 15

Abstract

Myeloproliferative neoplasms (MPNs) comprise a group of hematological disorders characterized by overproduction of blood cells caused by somatic driver mutations. While most MPN cases arise sporadically, familial clustering is increasingly recognized, occurring in around 7% of cases. Within affected families, different driver mutations ( JAK2, CALR, MPL ) and disease subtypes—including polycythemia vera, essential thrombocythemia, and myelofibrosis —can be observed [ 1 , 2 , 3 ]. Several germline variants increasing susceptibility to MPNs have been identified, including variants in JAK2 (‘46/1’ haplotype; 4-fold increased MPN risk) [ 4 ], TERT (2-fold), SH2B3, TET2, CHEK2, ATM, PINT , and GFI1B [ 3 , 5 , 6 , 7 ]. However, the underlying mechanisms by which these germline variants contribute to the acquisition of the somatic drivers remain unclear.

Fields of Study & Subjects

Myeloproliferative Neoplasms: Diagnosis and Treatment Acute Myeloid Leukemia Research Eosinophilic Disorders and Syndromes

Publication details

Journal / source
Blood Cancer Journal
Publisher
Springer Science and Business Media LLC
Volume
16
Issue
1
Pages
2–2
Publication date
5 January 2026
Language
EN