ASXL1 mutations, previous vascular complications and age at diagnosis predict survival in 85 WHO-defined polycythaemia vera patients

被引:13
作者
Andreasson, Bjorn [1 ]
Pettersson, Helna [1 ]
Wasslavik, Carina [2 ]
Johansson, Peter [3 ]
Palmqvist, Lars [2 ,4 ]
Asp, Julia [2 ,4 ]
机构
[1] NU Hosp Grp, Dept Med, Hematol Sect, Uddevalla, Sweden
[2] Sahlgrens Univ Hosp, Dept Clin Chem, Bruna Straket 16, S-41345 Gothenburg, Sweden
[3] Sahlgrens Univ Hosp, Dept Med, Haematol & Coagulat Sect, Gothenburg, Sweden
[4] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Lab Med, Gothenburg, Sweden
关键词
polycythaemia vera; myeloproliferative neoplasms; next-generation sequencing; survival; ASXL1; WORLD-HEALTH-ORGANIZATION; JAK2; EXON-12; MUTATIONS; PRIMARY MYELOFIBROSIS; PROGNOSIS; CLASSIFICATION; TRANSFORMATION; NEOPLASMS;
D O I
10.1111/bjh.16450
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Polycythaemia vera (PV) patients have an overall comparatively favourable prognosis, but disease progression is very heterogeneous and life-threatening thrombosis and bleedings are frequent complications in untreated disease. Moreover, transformation to more severe secondary myelofibrosis and acute myeloid leukaemia can occur. The aim of this study was to identify gene mutations that could be used together with clinical data as prognostic markers to guide treatment decisions in PV patients. A well-characterized WHO-defined cohort of PV patients was used. Clinical data and blood values were evaluated and a myeloid sequencing panel was used to screen for additional mutations other than the diagnostic JAK2 V617F and JAK2 exon 12 mutations. In 78% of the PV patients, at least one mutation additional to JAK2 V617F was detected. Additional mutations in genes coding for epigenetic modifiers, like TET2, DNMT3A and ASXL1, were most frequent. When correlated to overall survival, mutations in ASXL1 were significantly associated with inferior survival. In an attempt to obtain prognostic guidance in a larger number of patients, the presence of ASXL1 mutations was combined with age and vascular complications prior to diagnosis. Based on these data we were able to define three risk groups that predicted survival.
引用
收藏
页码:913 / 919
页数:7
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