Cargando…

Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) includes heterogeneous conditions such as previous history and specific cytogenetic and morphological properties. In this study, we analyze genetic aberrations using an RNA-based next-generation sequencing (NGS) panel assay in 45 p...

Descripción completa

Detalles Bibliográficos
Autores principales: Kang, Dain, Jung, Jin, Park, Silvia, Cho, Byung-Sik, Kim, Hee-Je, Kim, Yeojae, Lee, Jong-Mi, Kim, Hoon Seok, Ahn, Ari, Kim, Myungshin, Kim, Yonggoo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105081/
https://www.ncbi.nlm.nih.gov/pubmed/35566503
http://dx.doi.org/10.3390/jcm11092378
_version_ 1784707952848928768
author Kang, Dain
Jung, Jin
Park, Silvia
Cho, Byung-Sik
Kim, Hee-Je
Kim, Yeojae
Lee, Jong-Mi
Kim, Hoon Seok
Ahn, Ari
Kim, Myungshin
Kim, Yonggoo
author_facet Kang, Dain
Jung, Jin
Park, Silvia
Cho, Byung-Sik
Kim, Hee-Je
Kim, Yeojae
Lee, Jong-Mi
Kim, Hoon Seok
Ahn, Ari
Kim, Myungshin
Kim, Yonggoo
author_sort Kang, Dain
collection PubMed
description Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) includes heterogeneous conditions such as previous history and specific cytogenetic and morphological properties. In this study, we analyze genetic aberrations using an RNA-based next-generation sequencing (NGS) panel assay in 45 patients with AML-MRC and detect 4 gene fusions of KMT2A-SEPT9, KMT2A-ELL, NUP98-NSD1, and RUNX1-USP42 and 81 somatic mutations. Overall, all patients had genetic aberrations comprising of not only cytogenetic changes, but also gene fusions and mutations. We also demonstrated several characteristic genetic mutations according to the AML-MRC subgroup. TP53 was the most commonly mutated gene (n = 11, 24%) and all were found in the AML-MRC subgroup with myelodysplastic syndrome-defining cytogenetic abnormalities (AML-MRC-C) (p = 0.002). These patients showed extremely poor overall survival not only in AML-MRC, but also within the AML-MRC-C subgroup. The ASXL1 (n = 9, 20%) and SRSF2 (n = 7, 16%) mutations were associated with the AML-MRC subgroup with >50% dysplasia in at least two lineages (AML-MRC-M) and were frequently co-mutated (55%, 6/11, p < 0.001). Both mutations could be used as surrogate markers to diagnose AML-MRC, especially when the assessment of multilineage dysplasia was difficult. IDH1/IDH2 (n = 13, 29%) were most commonly mutated in AML-MRC, followed by CEBPA (n = 5, 11%), PTPN11 (n = 5, 11%), FLT3 (n = 4, 9%), IDH1 (n = 4, 9%), and RUNX1 (n = 4, 9%). These mutations were not limited in any AML-MRC subgroup and could have more significance as a risk factor or susceptibility marker for target therapy in not only AML-MRC, but also other AML categories.
format Online
Article
Text
id pubmed-9105081
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91050812022-05-14 Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes Kang, Dain Jung, Jin Park, Silvia Cho, Byung-Sik Kim, Hee-Je Kim, Yeojae Lee, Jong-Mi Kim, Hoon Seok Ahn, Ari Kim, Myungshin Kim, Yonggoo J Clin Med Article Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) includes heterogeneous conditions such as previous history and specific cytogenetic and morphological properties. In this study, we analyze genetic aberrations using an RNA-based next-generation sequencing (NGS) panel assay in 45 patients with AML-MRC and detect 4 gene fusions of KMT2A-SEPT9, KMT2A-ELL, NUP98-NSD1, and RUNX1-USP42 and 81 somatic mutations. Overall, all patients had genetic aberrations comprising of not only cytogenetic changes, but also gene fusions and mutations. We also demonstrated several characteristic genetic mutations according to the AML-MRC subgroup. TP53 was the most commonly mutated gene (n = 11, 24%) and all were found in the AML-MRC subgroup with myelodysplastic syndrome-defining cytogenetic abnormalities (AML-MRC-C) (p = 0.002). These patients showed extremely poor overall survival not only in AML-MRC, but also within the AML-MRC-C subgroup. The ASXL1 (n = 9, 20%) and SRSF2 (n = 7, 16%) mutations were associated with the AML-MRC subgroup with >50% dysplasia in at least two lineages (AML-MRC-M) and were frequently co-mutated (55%, 6/11, p < 0.001). Both mutations could be used as surrogate markers to diagnose AML-MRC, especially when the assessment of multilineage dysplasia was difficult. IDH1/IDH2 (n = 13, 29%) were most commonly mutated in AML-MRC, followed by CEBPA (n = 5, 11%), PTPN11 (n = 5, 11%), FLT3 (n = 4, 9%), IDH1 (n = 4, 9%), and RUNX1 (n = 4, 9%). These mutations were not limited in any AML-MRC subgroup and could have more significance as a risk factor or susceptibility marker for target therapy in not only AML-MRC, but also other AML categories. MDPI 2022-04-23 /pmc/articles/PMC9105081/ /pubmed/35566503 http://dx.doi.org/10.3390/jcm11092378 Text en © 2022 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
Kang, Dain
Jung, Jin
Park, Silvia
Cho, Byung-Sik
Kim, Hee-Je
Kim, Yeojae
Lee, Jong-Mi
Kim, Hoon Seok
Ahn, Ari
Kim, Myungshin
Kim, Yonggoo
Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes
title Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes
title_full Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes
title_fullStr Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes
title_full_unstemmed Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes
title_short Genetic Characteristics According to Subgroup of Acute Myeloid Leukemia with Myelodysplasia-Related Changes
title_sort genetic characteristics according to subgroup of acute myeloid leukemia with myelodysplasia-related changes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105081/
https://www.ncbi.nlm.nih.gov/pubmed/35566503
http://dx.doi.org/10.3390/jcm11092378
work_keys_str_mv AT kangdain geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges
AT jungjin geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges
AT parksilvia geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges
AT chobyungsik geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges
AT kimheeje geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges
AT kimyeojae geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges
AT leejongmi geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges
AT kimhoonseok geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges
AT ahnari geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges
AT kimmyungshin geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges
AT kimyonggoo geneticcharacteristicsaccordingtosubgroupofacutemyeloidleukemiawithmyelodysplasiarelatedchanges