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Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features

We report a 69-year-old female who was a human T-cell leukemia virus type 1 carrier and exhibited a unique clinical course of developing three hematological malignancies within a short period: diffuse large B-cell lymphoma (DLBCL), chronic myelomonocytic leukemia (CMMoL), and acute myeloid leukemia...

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Autores principales: Suzuki, Tomotaka, Yokomori, Rui, Sanda, Takaomi, Kikuchi, Takaki, Marumo, Yoshiaki, Kinoshita, Shiori, Narita, Tomoko, Masaki, Ayako, Ito, Asahi, Ri, Masaki, Kusumoto, Shigeru, Komatsu, Hirokazu, Inagaki, Hiroshi, Iida, Shinsuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981998/
https://www.ncbi.nlm.nih.gov/pubmed/36874114
http://dx.doi.org/10.3389/fonc.2023.1116418
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author Suzuki, Tomotaka
Yokomori, Rui
Sanda, Takaomi
Kikuchi, Takaki
Marumo, Yoshiaki
Kinoshita, Shiori
Narita, Tomoko
Masaki, Ayako
Ito, Asahi
Ri, Masaki
Kusumoto, Shigeru
Komatsu, Hirokazu
Inagaki, Hiroshi
Iida, Shinsuke
author_facet Suzuki, Tomotaka
Yokomori, Rui
Sanda, Takaomi
Kikuchi, Takaki
Marumo, Yoshiaki
Kinoshita, Shiori
Narita, Tomoko
Masaki, Ayako
Ito, Asahi
Ri, Masaki
Kusumoto, Shigeru
Komatsu, Hirokazu
Inagaki, Hiroshi
Iida, Shinsuke
author_sort Suzuki, Tomotaka
collection PubMed
description We report a 69-year-old female who was a human T-cell leukemia virus type 1 carrier and exhibited a unique clinical course of developing three hematological malignancies within a short period: diffuse large B-cell lymphoma (DLBCL), chronic myelomonocytic leukemia (CMMoL), and acute myeloid leukemia (AML). Although the blast cells in AML showed typical morphological and immunophenotypical features of acute promyelocytic leukemia (APL), it did not harbor RARα gene fusion and thus initially diagnosed as APL-like leukemia (APLL). The patient developed heart failure with a fulminant clinical course and died soon after the diagnosis of APLL. Retrospective analysis with whole-genome sequencing detected a chromosomal rearrangement between KMT2A and ACTN4 gene loci both in CMMoL and APLL samples, but not in the DLBCL sample. Therefore, CMMoL and APLL were considered to be derived from the same clone with KMT2A translocation associated with prior immunochemotherapy. However, KMT2A rearrangement is rarely found in CMMoL in general and ACTN4 is also a rare partner of KMT2A translocation. Thus, this case did not follow typical transformational process of CMMoL or KMT2A-rearranged leukemia. Importantly, additional genetic alterations, including NRAS G12 mutation, were found in APLL, but not in CMMoL samples, suggesting that they might contribute to leukemic transformation. This report highlights the diverse effects of KMT2A translocation and NRAS mutation on the transformation of hematological cells as well as the importance of upfront sequencing analysis to detect genetic backgrounds for a better understanding of therapy-related leukemia.
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spelling pubmed-99819982023-03-04 Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features Suzuki, Tomotaka Yokomori, Rui Sanda, Takaomi Kikuchi, Takaki Marumo, Yoshiaki Kinoshita, Shiori Narita, Tomoko Masaki, Ayako Ito, Asahi Ri, Masaki Kusumoto, Shigeru Komatsu, Hirokazu Inagaki, Hiroshi Iida, Shinsuke Front Oncol Oncology We report a 69-year-old female who was a human T-cell leukemia virus type 1 carrier and exhibited a unique clinical course of developing three hematological malignancies within a short period: diffuse large B-cell lymphoma (DLBCL), chronic myelomonocytic leukemia (CMMoL), and acute myeloid leukemia (AML). Although the blast cells in AML showed typical morphological and immunophenotypical features of acute promyelocytic leukemia (APL), it did not harbor RARα gene fusion and thus initially diagnosed as APL-like leukemia (APLL). The patient developed heart failure with a fulminant clinical course and died soon after the diagnosis of APLL. Retrospective analysis with whole-genome sequencing detected a chromosomal rearrangement between KMT2A and ACTN4 gene loci both in CMMoL and APLL samples, but not in the DLBCL sample. Therefore, CMMoL and APLL were considered to be derived from the same clone with KMT2A translocation associated with prior immunochemotherapy. However, KMT2A rearrangement is rarely found in CMMoL in general and ACTN4 is also a rare partner of KMT2A translocation. Thus, this case did not follow typical transformational process of CMMoL or KMT2A-rearranged leukemia. Importantly, additional genetic alterations, including NRAS G12 mutation, were found in APLL, but not in CMMoL samples, suggesting that they might contribute to leukemic transformation. This report highlights the diverse effects of KMT2A translocation and NRAS mutation on the transformation of hematological cells as well as the importance of upfront sequencing analysis to detect genetic backgrounds for a better understanding of therapy-related leukemia. Frontiers Media S.A. 2023-02-17 /pmc/articles/PMC9981998/ /pubmed/36874114 http://dx.doi.org/10.3389/fonc.2023.1116418 Text en Copyright © 2023 Suzuki, Yokomori, Sanda, Kikuchi, Marumo, Kinoshita, Narita, Masaki, Ito, Ri, Kusumoto, Komatsu, Inagaki and Iida https://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(s) 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
Suzuki, Tomotaka
Yokomori, Rui
Sanda, Takaomi
Kikuchi, Takaki
Marumo, Yoshiaki
Kinoshita, Shiori
Narita, Tomoko
Masaki, Ayako
Ito, Asahi
Ri, Masaki
Kusumoto, Shigeru
Komatsu, Hirokazu
Inagaki, Hiroshi
Iida, Shinsuke
Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features
title Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features
title_full Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features
title_fullStr Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features
title_full_unstemmed Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features
title_short Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features
title_sort case report: genomic analysis of a therapy-related chronic myelomonocytic leukemia with kmt2a rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981998/
https://www.ncbi.nlm.nih.gov/pubmed/36874114
http://dx.doi.org/10.3389/fonc.2023.1116418
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