Abstract:
:Myeloproliferative neoplasms (MPNs) are a group of clonal disorders characterized by aberrant hematopoietic proliferation and an increased tendency toward leukemic transformation. We used targeted next-generation sequencing (NGS) of 104 genes to detect somatic mutations in a cohort of 197 MPN patients and followed clonal evolution and the impact on clinical outcome. Mutations in calreticulin (CALR) were detected using a sensitive allele-specific polymerase chain reaction. We observed somatic mutations in 90% of patients, and 37% carried somatic mutations other than JAK2 V617F and CALR. The presence of 2 or more somatic mutations significantly reduced overall survival and increased the risk of transformation into acute myeloid leukemia. In particular, somatic mutations with loss of heterozygosity in TP53 were strongly associated with leukemic transformation. We used NGS to follow and quantitate somatic mutations in serial samples from MPN patients. Surprisingly, the number of mutations between early and late patient samples did not significantly change, and during a total follow-up of 133 patient years, only 2 new mutations appeared, suggesting that the mutation rate in MPN is rather low. Our data show that comprehensive mutational screening at diagnosis and during follow-up has considerable potential to identify patients at high risk of disease progression.
journal_name
Bloodjournal_title
Bloodauthors
Lundberg P,Karow A,Nienhold R,Looser R,Hao-Shen H,Nissen I,Girsberger S,Lehmann T,Passweg J,Stern M,Beisel C,Kralovics R,Skoda RCdoi
10.1182/blood-2013-11-537167subject
Has Abstractpub_date
2014-04-03 00:00:00pages
2220-8issue
14eissn
0006-4971issn
1528-0020pii
blood-2013-11-537167journal_volume
123pub_type
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