Cargando…

UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia

Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with...

Descripción completa

Detalles Bibliográficos
Autores principales: Duployez, Nicolas, Vasseur, Loïc, Kim, Rathana, Largeaud, Laëtitia, Passet, Marie, L’Haridon, Anaïs, Lemaire, Pierre, Fenwarth, Laurène, Geffroy, Sandrine, Helevaut, Nathalie, Celli‑Lebras, Karine, Adès, Lionel, Lebon, Delphine, Berthon, Céline, Marceau-Renaut, Alice, Cheok, Meyling, Lambert, Juliette, Récher, Christian, Raffoux, Emmanuel, Micol, Jean-Baptiste, Pigneux, Arnaud, Gardin, Claude, Delabesse, Eric, Soulier, Jean, Hunault, Mathilde, Dombret, Hervé, Itzykson, Raphael, Clappier, Emmanuelle, Preudhomme, Claude
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244165/
https://www.ncbi.nlm.nih.gov/pubmed/37085611
http://dx.doi.org/10.1038/s41375-023-01906-z
_version_ 1785054576162897920
author Duployez, Nicolas
Vasseur, Loïc
Kim, Rathana
Largeaud, Laëtitia
Passet, Marie
L’Haridon, Anaïs
Lemaire, Pierre
Fenwarth, Laurène
Geffroy, Sandrine
Helevaut, Nathalie
Celli‑Lebras, Karine
Adès, Lionel
Lebon, Delphine
Berthon, Céline
Marceau-Renaut, Alice
Cheok, Meyling
Lambert, Juliette
Récher, Christian
Raffoux, Emmanuel
Micol, Jean-Baptiste
Pigneux, Arnaud
Gardin, Claude
Delabesse, Eric
Soulier, Jean
Hunault, Mathilde
Dombret, Hervé
Itzykson, Raphael
Clappier, Emmanuelle
Preudhomme, Claude
author_facet Duployez, Nicolas
Vasseur, Loïc
Kim, Rathana
Largeaud, Laëtitia
Passet, Marie
L’Haridon, Anaïs
Lemaire, Pierre
Fenwarth, Laurène
Geffroy, Sandrine
Helevaut, Nathalie
Celli‑Lebras, Karine
Adès, Lionel
Lebon, Delphine
Berthon, Céline
Marceau-Renaut, Alice
Cheok, Meyling
Lambert, Juliette
Récher, Christian
Raffoux, Emmanuel
Micol, Jean-Baptiste
Pigneux, Arnaud
Gardin, Claude
Delabesse, Eric
Soulier, Jean
Hunault, Mathilde
Dombret, Hervé
Itzykson, Raphael
Clappier, Emmanuelle
Preudhomme, Claude
author_sort Duployez, Nicolas
collection PubMed
description Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3-ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence of FLT3-ITD. UBTF-TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) than UBTF-wild-type patients. In patients enrolled in the ALFA-0702 study (n = 614 patients including 21 with UBTF-TD AML), the 3-year disease-free survival (DFS) and overall survival of UBTF-TD patients were 42.9% (95%CI: 23.4–78.5%) and 57.1% (95%CI: 39.5–82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests that WT1-mutated clones are frequently selected under ICT. This study supports the recognition of UBTF-TD AML as a new AML entity in adults. [Image: see text]
format Online
Article
Text
id pubmed-10244165
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-102441652023-06-08 UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia Duployez, Nicolas Vasseur, Loïc Kim, Rathana Largeaud, Laëtitia Passet, Marie L’Haridon, Anaïs Lemaire, Pierre Fenwarth, Laurène Geffroy, Sandrine Helevaut, Nathalie Celli‑Lebras, Karine Adès, Lionel Lebon, Delphine Berthon, Céline Marceau-Renaut, Alice Cheok, Meyling Lambert, Juliette Récher, Christian Raffoux, Emmanuel Micol, Jean-Baptiste Pigneux, Arnaud Gardin, Claude Delabesse, Eric Soulier, Jean Hunault, Mathilde Dombret, Hervé Itzykson, Raphael Clappier, Emmanuelle Preudhomme, Claude Leukemia Article Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18–60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3-ITDs (51%) and trisomy 8 (29%). BM morphology frequently demonstrates dysmyelopoiesis albeit modulated by the co-occurrence of FLT3-ITD. UBTF-TD patients have lower complete remission (CR) rates (57% after 1 course and 76% after 2 courses of intensive chemotherapy [ICT]) than UBTF-wild-type patients. In patients enrolled in the ALFA-0702 study (n = 614 patients including 21 with UBTF-TD AML), the 3-year disease-free survival (DFS) and overall survival of UBTF-TD patients were 42.9% (95%CI: 23.4–78.5%) and 57.1% (95%CI: 39.5–82.8%) and did not significantly differ from those of ELN 2022 intermediate/adverse risk patients. Finally, the study of paired diagnosis and relapsed/refractory AML samples suggests that WT1-mutated clones are frequently selected under ICT. This study supports the recognition of UBTF-TD AML as a new AML entity in adults. [Image: see text] Nature Publishing Group UK 2023-04-21 2023 /pmc/articles/PMC10244165/ /pubmed/37085611 http://dx.doi.org/10.1038/s41375-023-01906-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Duployez, Nicolas
Vasseur, Loïc
Kim, Rathana
Largeaud, Laëtitia
Passet, Marie
L’Haridon, Anaïs
Lemaire, Pierre
Fenwarth, Laurène
Geffroy, Sandrine
Helevaut, Nathalie
Celli‑Lebras, Karine
Adès, Lionel
Lebon, Delphine
Berthon, Céline
Marceau-Renaut, Alice
Cheok, Meyling
Lambert, Juliette
Récher, Christian
Raffoux, Emmanuel
Micol, Jean-Baptiste
Pigneux, Arnaud
Gardin, Claude
Delabesse, Eric
Soulier, Jean
Hunault, Mathilde
Dombret, Hervé
Itzykson, Raphael
Clappier, Emmanuelle
Preudhomme, Claude
UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
title UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
title_full UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
title_fullStr UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
title_full_unstemmed UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
title_short UBTF tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
title_sort ubtf tandem duplications define a distinct subtype of adult de novo acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244165/
https://www.ncbi.nlm.nih.gov/pubmed/37085611
http://dx.doi.org/10.1038/s41375-023-01906-z
work_keys_str_mv AT duployeznicolas ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT vasseurloic ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT kimrathana ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT largeaudlaetitia ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT passetmarie ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT lharidonanais ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT lemairepierre ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT fenwarthlaurene ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT geffroysandrine ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT helevautnathalie ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT cellilebraskarine ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT adeslionel ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT lebondelphine ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT berthonceline ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT marceaurenautalice ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT cheokmeyling ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT lambertjuliette ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT recherchristian ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT raffouxemmanuel ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT micoljeanbaptiste ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT pigneuxarnaud ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT gardinclaude ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT delabesseeric ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT soulierjean ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT hunaultmathilde ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT dombretherve ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT itzyksonraphael ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT clappieremmanuelle ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia
AT preudhommeclaude ubtftandemduplicationsdefineadistinctsubtypeofadultdenovoacutemyeloidleukemia