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Sequential mutational evaluation of CALR ‐mutated myeloproliferative neoplasms with thrombocytosis reveals an association between CALR allele burden evolution and disease progression
Author(s) -
Cottin Laurane,
Riou Jérémie,
Orvain Corentin,
Ianotto Jean Christophe,
Boyer Françoise,
Renard Maxime,
TruchanGraczyk Matgorzata,
Murati Anne,
JouanneauCourville Rébecca,
Allangba Olivier,
Mansier Olivier,
Burroni Barbara,
Rousselet Marie-Christine,
QuintinRoué Isabelle,
Martin Antoine,
SadotLebouvier Sophie,
Delneste Yves,
Chrétien JeanMarie,
HunaultBerger Mathilde,
Blanchet Odile,
Lippert Eric,
Ugo Valérie,
Luque Paz Damien
Publication year - 2020
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16276
Subject(s) - myelofibrosis , allele , medicine , thrombocytosis , myeloproliferative neoplasm , oncology , myeloid , disease , genetics , bone marrow , gastroenterology , gene , biology , platelet
Summary In myeloproliferative neoplasms (MPN), JAK2 V617F allele burden measurement has an impact on prognosis that helps in patient monitoring. Less is known about its usefulness in CALR ‐mutated cases. Additional mutations found by next‐generation sequencing have also shown an impact on prognosis that may drive therapeutic choices, especially in myelofibrosis, but few studies focused on CALR ‐mutated patients. We performed a molecular evaluation combining next‐generation sequencing with a myeloid panel and CALR allele burden measurement at diagnosis and during follow‐up in a cohort of 45 patients with CALR ‐mutated essential thrombocythaemia. The bone marrow histology was also blindly reviewed in order to apply the WHO2016 classification. The most frequently mutated gene was TET2 (11/21 mutations). CALR type 1‐like patients appear to have a more complex molecular landscape. We found an association between disease progression and CALR allele burden increase during follow‐up, independently of additional mutations and WHO2016‐reviewed diagnosis. Patients with disease progression at the time of follow‐up showed a significant increase in CALR allele burden (+16·7%, P = 0·005) whereas patients without disease progression had a stable allele burden (+3·7%, P = 0·194). This result argues for clinical interest in CALR allele burden monitoring.