Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident
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 a...
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| Format: | Article |
| Language: | English |
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Wiley
2020
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| Online Access: | https://hdl.handle.net/1721.1/126343 |
| _version_ | 1826201376340836352 |
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| author | Adam, Miriam Fraenkel, Ernest |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Adam, Miriam Fraenkel, Ernest |
| author_sort | Adam, Miriam |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:50:37Z |
| format | Article |
| id | mit-1721.1/126343 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:50:37Z |
| publishDate | 2020 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1263432022-09-27T22:20:02Z Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident Adam, Miriam Fraenkel, Ernest Massachusetts Institute of Technology. Department of Biological Engineering 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. United States. Army Research Office. Institute for Collaborative Biotechnologies (Grant W9111NF-09–001) 2020-07-23T15:45:11Z 2020-07-23T15:45:11Z 2019-01 2020-03-06T15:28:54Z Article http://purl.org/eprint/type/JournalArticle 0361-8609 1096-8652 https://hdl.handle.net/1721.1/126343 Poluben, Larysa et al. “Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident.” American journal of hematology, vol. 94, no. 1, 2019, pp. 62-73 © 2019 The Author(s) en 10.1002/AJH.25307 American journal of hematology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley PMC |
| spellingShingle | Adam, Miriam Fraenkel, Ernest Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident |
| title | Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident |
| title_full | Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident |
| title_fullStr | Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident |
| title_full_unstemmed | Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident |
| title_short | Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident |
| title_sort | characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the chernobyl nuclear accident |
| url | https://hdl.handle.net/1721.1/126343 |
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