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Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations

JAK2 (Janus kinase 2) V617F, CALR (Calreticulin) exon 9, and MPL (receptor for thrombopoietin) exon 10 mutations are associated with the vast majority of Ph-negative chronic myeloproliferative neoplasms (MPNs). These mutations affect sequential stages of proliferative signal transduction and therefo...

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Autores principales: Makarik, Tatiana V., Abdullaev, Adhamjon O., Nikulina, Elena E., Treglazova, Svetlana A., Stepanova, Elena E., Subortseva, Irina N., Kovrigina, Alla M., Melikyan, Anait L., Kulikov, Sergei M., Sudarikov, Andrey B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069892/
https://www.ncbi.nlm.nih.gov/pubmed/33921387
http://dx.doi.org/10.3390/genes12040559
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author Makarik, Tatiana V.
Abdullaev, Adhamjon O.
Nikulina, Elena E.
Treglazova, Svetlana A.
Stepanova, Elena E.
Subortseva, Irina N.
Kovrigina, Alla M.
Melikyan, Anait L.
Kulikov, Sergei M.
Sudarikov, Andrey B.
author_facet Makarik, Tatiana V.
Abdullaev, Adhamjon O.
Nikulina, Elena E.
Treglazova, Svetlana A.
Stepanova, Elena E.
Subortseva, Irina N.
Kovrigina, Alla M.
Melikyan, Anait L.
Kulikov, Sergei M.
Sudarikov, Andrey B.
author_sort Makarik, Tatiana V.
collection PubMed
description JAK2 (Janus kinase 2) V617F, CALR (Calreticulin) exon 9, and MPL (receptor for thrombopoietin) exon 10 mutations are associated with the vast majority of Ph-negative chronic myeloproliferative neoplasms (MPNs). These mutations affect sequential stages of proliferative signal transduction and therefore, after the emergence of one type of mutation, other types should not have any selective advantages for clonal expansion. However, simultaneous findings of these mutations have been reported by different investigators in up to 10% of MPN cases. Our study includes DNA samples from 1958 patients with clinical evidence of MPN, admitted to the National Research Center for Hematology for genetic analysis between 2016 and 2019. In 315 of 1402 cases (22.6%), CALR mutations were detected. In 23 of these 315 cases (7.3%), the JAK2 V617F mutation was found in addition to the CALR mutation. In 16 from 24 (69.6%) cases, with combined CALR and JAK2 mutations, V617F allele burden was lower than 1%. A combination of JAK2 V617F with MPL W515L/K was also observed in 1 out of 1348 cases, only. JAK2 allele burden in this case was also lower than 1%. Additional mutations may coexist over the low background of JAK2 V617F allele. Therefore, in cases of detecting MPNs with a low allelic load JAK2 V617F, it may be advisable to search for other molecular markers, primarily mutations in exon 9 of CALR. The load of the combined mutations measured at different time points may indicate that, at least in some cases, these mutations could be represented by different clones of malignant cells.
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spelling pubmed-80698922021-04-26 Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations Makarik, Tatiana V. Abdullaev, Adhamjon O. Nikulina, Elena E. Treglazova, Svetlana A. Stepanova, Elena E. Subortseva, Irina N. Kovrigina, Alla M. Melikyan, Anait L. Kulikov, Sergei M. Sudarikov, Andrey B. Genes (Basel) Article JAK2 (Janus kinase 2) V617F, CALR (Calreticulin) exon 9, and MPL (receptor for thrombopoietin) exon 10 mutations are associated with the vast majority of Ph-negative chronic myeloproliferative neoplasms (MPNs). These mutations affect sequential stages of proliferative signal transduction and therefore, after the emergence of one type of mutation, other types should not have any selective advantages for clonal expansion. However, simultaneous findings of these mutations have been reported by different investigators in up to 10% of MPN cases. Our study includes DNA samples from 1958 patients with clinical evidence of MPN, admitted to the National Research Center for Hematology for genetic analysis between 2016 and 2019. In 315 of 1402 cases (22.6%), CALR mutations were detected. In 23 of these 315 cases (7.3%), the JAK2 V617F mutation was found in addition to the CALR mutation. In 16 from 24 (69.6%) cases, with combined CALR and JAK2 mutations, V617F allele burden was lower than 1%. A combination of JAK2 V617F with MPL W515L/K was also observed in 1 out of 1348 cases, only. JAK2 allele burden in this case was also lower than 1%. Additional mutations may coexist over the low background of JAK2 V617F allele. Therefore, in cases of detecting MPNs with a low allelic load JAK2 V617F, it may be advisable to search for other molecular markers, primarily mutations in exon 9 of CALR. The load of the combined mutations measured at different time points may indicate that, at least in some cases, these mutations could be represented by different clones of malignant cells. MDPI 2021-04-12 /pmc/articles/PMC8069892/ /pubmed/33921387 http://dx.doi.org/10.3390/genes12040559 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Makarik, Tatiana V.
Abdullaev, Adhamjon O.
Nikulina, Elena E.
Treglazova, Svetlana A.
Stepanova, Elena E.
Subortseva, Irina N.
Kovrigina, Alla M.
Melikyan, Anait L.
Kulikov, Sergei M.
Sudarikov, Andrey B.
Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations
title Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations
title_full Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations
title_fullStr Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations
title_full_unstemmed Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations
title_short Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations
title_sort low jak2 v617f allele burden in ph-negative chronic myeloproliferative neoplasms is associated with additional calr or mpl gene mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069892/
https://www.ncbi.nlm.nih.gov/pubmed/33921387
http://dx.doi.org/10.3390/genes12040559
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