Genetic alterations in essential thrombocythemia progression to acute myeloid leukemia: A case series and review of the literature

Jackline P. Ayres-Silva, Martin H. Bonamino, Maria E. Gouveia, Barbara C.R. Monte-Mor, Diego F. Coutinho, Adelmo H. Daumas, Cristiana Solza, Esteban D Braggio, Ilana Renault Zalcberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number32
JournalFrontiers in Oncology
Volume8
Issue numberFEB
DOIs
StatePublished - Feb 19 2018

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Essential Thrombocythemia
Acute Myeloid Leukemia
Exome
Comparative Genomic Hybridization
Chromosome Aberrations
Neoplasms
Thrombocytosis
Frameshift Mutation
Hydroxyurea
Myelodysplastic Syndromes
Missense Mutation
Disease Progression

Keywords

  • +2p
  • Array-based comparative genomic hybridization
  • Essential thrombocythemia
  • Myeloproliferative neoplasms
  • Secondary acute myeloid leukemia
  • Whole exome sequencing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ayres-Silva, J. P., Bonamino, M. H., Gouveia, M. E., Monte-Mor, B. C. R., Coutinho, D. F., Daumas, A. H., ... Zalcberg, I. R. (2018). Genetic alterations in essential thrombocythemia progression to acute myeloid leukemia: A case series and review of the literature. Frontiers in Oncology, 8(FEB), [32]. https://doi.org/10.3389/fonc.2018.00032

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 D; Zalcberg, Ilana Renault.

In: Frontiers in Oncology, Vol. 8, No. FEB, 32, 19.02.2018.

Research output: Contribution to journalArticle

Ayres-Silva, JP, Bonamino, MH, Gouveia, ME, Monte-Mor, BCR, Coutinho, DF, Daumas, AH, Solza, C, Braggio, ED & Zalcberg, IR 2018, 'Genetic alterations in essential thrombocythemia progression to acute myeloid leukemia: A case series and review of the literature', Frontiers in Oncology, vol. 8, no. FEB, 32. https://doi.org/10.3389/fonc.2018.00032
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 D ; Zalcberg, Ilana Renault. / Genetic alterations in essential thrombocythemia progression to acute myeloid leukemia : A case series and review of the literature. In: Frontiers in Oncology. 2018 ; Vol. 8, No. FEB.
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abstract = "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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AU - Coutinho, Diego F.

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