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Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature

The genetic events associated with transformation of myeloproliferative neoplasms (MPNs) to secondary acute myeloid leukemia (sAML), particularly in the subgroup of essential thrombocythemia (ET) patients, remain incompletely understood. Deep studies using high-throughput methods might lead to a bet...

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Autores principales: Ayres-Silva, Jackline P., Bonamino, Martin H., Gouveia, Maria E., Monte-Mor, Barbara C. R., Coutinho, Diego F., Daumas, Adelmo H., Solza, Cristiana, Braggio, Esteban, Zalcberg, Ilana Renault
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826070/
https://www.ncbi.nlm.nih.gov/pubmed/29515972
http://dx.doi.org/10.3389/fonc.2018.00032
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author Ayres-Silva, Jackline P.
Bonamino, Martin H.
Gouveia, Maria E.
Monte-Mor, Barbara C. R.
Coutinho, Diego F.
Daumas, Adelmo H.
Solza, Cristiana
Braggio, Esteban
Zalcberg, Ilana Renault
author_facet Ayres-Silva, Jackline P.
Bonamino, Martin H.
Gouveia, Maria E.
Monte-Mor, Barbara C. R.
Coutinho, Diego F.
Daumas, Adelmo H.
Solza, Cristiana
Braggio, Esteban
Zalcberg, Ilana Renault
author_sort Ayres-Silva, Jackline P.
collection PubMed
description The genetic events associated with transformation of myeloproliferative neoplasms (MPNs) to secondary acute myeloid leukemia (sAML), particularly in the subgroup of essential thrombocythemia (ET) patients, remain incompletely understood. Deep studies using high-throughput methods might lead to a better understanding of genetic landscape of ET patients who transformed to sAML. We performed array-based comparative genomic hybridization (aCGH) and whole exome sequencing (WES) to analyze paired samples from ET and sAML phases. We investigated five patients with previous history of MPN, which four had initial diagnosis of ET (one case harboring JAK2 p.Val617Phe and the remaining three CALR type II p.Lys385fs*47), and one was diagnosed with MPN/myelodysplastic syndrome with thrombocytosis (SF3B1 p.Lys700Glu). All were homogeneously treated with hydroxyurea, but subsequently transformed to sAML (mean time of 6 years/median of 4 years to transformation). Two of them have chromosomal abnormalities, and both acquire 2p gain and 5q deletion at sAML stage. The molecular mechanisms associated with leukemic progression in MPN patients are not clear. Our WES data showed TP53 alterations recurrently observed as mutations (missense and frameshift) and monoallelic loss. On the other hand, aCGH showed novel chromosome abnormalities (+2p and del5q) potentially associated with disease progression. The results reported here add valuable information to the still fragmented molecular basis of ET to sAML evolution. Further studies are necessary to identify minimal deleted/amplified region and genes relevant to sAML transformation.
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spelling pubmed-58260702018-03-07 Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature Ayres-Silva, Jackline P. Bonamino, Martin H. Gouveia, Maria E. Monte-Mor, Barbara C. R. Coutinho, Diego F. Daumas, Adelmo H. Solza, Cristiana Braggio, Esteban Zalcberg, Ilana Renault Front Oncol Oncology The genetic events associated with transformation of myeloproliferative neoplasms (MPNs) to secondary acute myeloid leukemia (sAML), particularly in the subgroup of essential thrombocythemia (ET) patients, remain incompletely understood. Deep studies using high-throughput methods might lead to a better understanding of genetic landscape of ET patients who transformed to sAML. We performed array-based comparative genomic hybridization (aCGH) and whole exome sequencing (WES) to analyze paired samples from ET and sAML phases. We investigated five patients with previous history of MPN, which four had initial diagnosis of ET (one case harboring JAK2 p.Val617Phe and the remaining three CALR type II p.Lys385fs*47), and one was diagnosed with MPN/myelodysplastic syndrome with thrombocytosis (SF3B1 p.Lys700Glu). All were homogeneously treated with hydroxyurea, but subsequently transformed to sAML (mean time of 6 years/median of 4 years to transformation). Two of them have chromosomal abnormalities, and both acquire 2p gain and 5q deletion at sAML stage. The molecular mechanisms associated with leukemic progression in MPN patients are not clear. Our WES data showed TP53 alterations recurrently observed as mutations (missense and frameshift) and monoallelic loss. On the other hand, aCGH showed novel chromosome abnormalities (+2p and del5q) potentially associated with disease progression. The results reported here add valuable information to the still fragmented molecular basis of ET to sAML evolution. Further studies are necessary to identify minimal deleted/amplified region and genes relevant to sAML transformation. Frontiers Media S.A. 2018-02-19 /pmc/articles/PMC5826070/ /pubmed/29515972 http://dx.doi.org/10.3389/fonc.2018.00032 Text en Copyright © 2018 Ayres-Silva, Bonamino, Gouveia, Monte-Mor, Coutinho, Daumas, Solza, Braggio and Zalcberg. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Ayres-Silva, Jackline P.
Bonamino, Martin H.
Gouveia, Maria E.
Monte-Mor, Barbara C. R.
Coutinho, Diego F.
Daumas, Adelmo H.
Solza, Cristiana
Braggio, Esteban
Zalcberg, Ilana Renault
Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature
title Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature
title_full Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature
title_fullStr Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature
title_full_unstemmed Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature
title_short Genetic Alterations in Essential Thrombocythemia Progression to Acute Myeloid Leukemia: A Case Series and Review of the Literature
title_sort genetic alterations in essential thrombocythemia progression to acute myeloid leukemia: a case series and review of the literature
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826070/
https://www.ncbi.nlm.nih.gov/pubmed/29515972
http://dx.doi.org/10.3389/fonc.2018.00032
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