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Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident
Author(s) -
Poluben Larysa,
Puligandla Maneka,
Neuberg Donna,
Bryke Christine R.,
Hsu Yahsuan,
Shumeiko Oleksandr,
Yuan Xin,
Voznesensky Olga,
Pihan German,
Adam Miriam,
Fraenkel Ernest,
Rasnic Roni,
Linial Michal,
Klymenko Sergiy,
Balk Steven P.,
Fraenkel Paula G.
Publication year - 2019
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.25307
Subject(s) - sanger sequencing , exact test , loss of heterozygosity , biology , medicine , microbiology and biotechnology , mutation , genetics , allele , gene
Abstract Myeloproliferative neoplasms (MPNs) driver mutations are usually found in JAK2 , MPL , and CALR genes; however, 10%‐15% of cases are triple negative (TN). A previous study showed lower rate of JAK2 V617F in primary myelofibrosis patients exposed to low doses of ionizing radiation (IR) from Chernobyl accident. To examine distinct driver mutations, we enrolled 281 Ukrainian IR‐exposed and unexposed MPN patients. Genomic DNA was obtained from peripheral blood leukocytes. JAK2 V617F, MPL W515, types 1‐ and 2‐like CALR mutations were identified by Sanger Sequencing and real time polymerase chain reaction. Chromosomal alterations were assessed by oligo‐SNP microarray platform. Additional genetic variants were identified by whole exome and targeted sequencing. Statistical significance was evaluated by Fisher's exact test and Wilcoxon's rank sum test (R, version 3.4.2). IR‐exposed MPN patients exhibited a different genetic profile vs unexposed: lower rate of JAK2 V617F (58.4% vs 75.4%, P = .0077), higher rate of type 1‐like CALR mutation (12.2% vs 3.1%, P = .0056), higher rate of TN cases (27.8% vs 16.2%, P = .0366), higher rate of potentially pathogenic sequence variants (mean numbers: 4.8 vs 3.1, P = .0242). Furthermore, we identified several potential drivers specific to IR‐exposed TN MPN patients: ATM p.S1691R with copy‐neutral loss of heterozygosity at 11q; EZH2 p.D659G at 7q and SUZ12 p.V71 M at 17q with copy number loss. Thus, IR‐exposed MPN patients represent a group with distinct genomic characteristics worthy of further study.