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Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins

T-cell acute lymphoblastic leukemias (T-ALL) represent 15% of pediatric and 25% of adult ALL. Since they have a particularly poor outcome in relapsed/refractory cases, identifying prognosis factors at diagnosis is crucial to adapting treatment for high-risk patients. Unlike acute myeloid leukemia an...

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Autores principales: Steimlé, Thomas, Dourthe, Marie-Emilie, Alcantara, Marion, Touzart, Aurore, Simonin, Mathieu, Mondesir, Johanna, Lhermitte, Ludovic, Bond, Jonathan, Graux, Carlos, Grardel, Nathalie, Cayuela, Jean-Michel, Arnoux, Isabelle, Gandemer, Virginie, Balsat, Marie, Vey, Norbert, Macintyre, Elizabeth, Ifrah, Norbert, Dombret, Hervé, Petit, Arnaud, Baruchel, André, Ruminy, Philippe, Boissel, Nicolas, Asnafi, Vahid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791998/
https://www.ncbi.nlm.nih.gov/pubmed/35082269
http://dx.doi.org/10.1038/s41408-022-00613-9
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author Steimlé, Thomas
Dourthe, Marie-Emilie
Alcantara, Marion
Touzart, Aurore
Simonin, Mathieu
Mondesir, Johanna
Lhermitte, Ludovic
Bond, Jonathan
Graux, Carlos
Grardel, Nathalie
Cayuela, Jean-Michel
Arnoux, Isabelle
Gandemer, Virginie
Balsat, Marie
Vey, Norbert
Macintyre, Elizabeth
Ifrah, Norbert
Dombret, Hervé
Petit, Arnaud
Baruchel, André
Ruminy, Philippe
Boissel, Nicolas
Asnafi, Vahid
author_facet Steimlé, Thomas
Dourthe, Marie-Emilie
Alcantara, Marion
Touzart, Aurore
Simonin, Mathieu
Mondesir, Johanna
Lhermitte, Ludovic
Bond, Jonathan
Graux, Carlos
Grardel, Nathalie
Cayuela, Jean-Michel
Arnoux, Isabelle
Gandemer, Virginie
Balsat, Marie
Vey, Norbert
Macintyre, Elizabeth
Ifrah, Norbert
Dombret, Hervé
Petit, Arnaud
Baruchel, André
Ruminy, Philippe
Boissel, Nicolas
Asnafi, Vahid
author_sort Steimlé, Thomas
collection PubMed
description T-cell acute lymphoblastic leukemias (T-ALL) represent 15% of pediatric and 25% of adult ALL. Since they have a particularly poor outcome in relapsed/refractory cases, identifying prognosis factors at diagnosis is crucial to adapting treatment for high-risk patients. Unlike acute myeloid leukemia and BCP ALL, chromosomal rearrangements leading to chimeric fusion-proteins with strong prognosis impact are sparsely reported in T-ALL. To address this issue an RT-MPLA assay was applied to a consecutive series of 522 adult and pediatric T-ALLs and identified a fusion transcript in 20% of cases. PICALM-MLLT10 (4%, n = 23), NUP214-ABL1 (3%, n = 19) and SET-NUP214 (3%, n = 18) were the most frequent. The clinico-biological characteristics linked to fusion transcripts in a subset of 235 patients (138 adults in the GRAALL2003/05 trials and 97 children from the FRALLE2000 trial) were analyzed to identify their prognosis impact. Patients with HOXA trans-deregulated T-ALLs with MLLT10, KMT2A and SET fusion transcripts (17%, 39/235) had a worse prognosis with a 5-year EFS of 35.7% vs 63.7% (HR = 1.63; p = 0.04) and a trend for a higher cumulative incidence of relapse (5-year CIR = 45.7% vs 25.2%, HR = 1.6; p = 0.11). Fusion transcripts status in T-ALL can be robustly identified by RT-MLPA, facilitating risk adapted treatment strategies for high-risk patients.
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spelling pubmed-87919982022-02-07 Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins Steimlé, Thomas Dourthe, Marie-Emilie Alcantara, Marion Touzart, Aurore Simonin, Mathieu Mondesir, Johanna Lhermitte, Ludovic Bond, Jonathan Graux, Carlos Grardel, Nathalie Cayuela, Jean-Michel Arnoux, Isabelle Gandemer, Virginie Balsat, Marie Vey, Norbert Macintyre, Elizabeth Ifrah, Norbert Dombret, Hervé Petit, Arnaud Baruchel, André Ruminy, Philippe Boissel, Nicolas Asnafi, Vahid Blood Cancer J Article T-cell acute lymphoblastic leukemias (T-ALL) represent 15% of pediatric and 25% of adult ALL. Since they have a particularly poor outcome in relapsed/refractory cases, identifying prognosis factors at diagnosis is crucial to adapting treatment for high-risk patients. Unlike acute myeloid leukemia and BCP ALL, chromosomal rearrangements leading to chimeric fusion-proteins with strong prognosis impact are sparsely reported in T-ALL. To address this issue an RT-MPLA assay was applied to a consecutive series of 522 adult and pediatric T-ALLs and identified a fusion transcript in 20% of cases. PICALM-MLLT10 (4%, n = 23), NUP214-ABL1 (3%, n = 19) and SET-NUP214 (3%, n = 18) were the most frequent. The clinico-biological characteristics linked to fusion transcripts in a subset of 235 patients (138 adults in the GRAALL2003/05 trials and 97 children from the FRALLE2000 trial) were analyzed to identify their prognosis impact. Patients with HOXA trans-deregulated T-ALLs with MLLT10, KMT2A and SET fusion transcripts (17%, 39/235) had a worse prognosis with a 5-year EFS of 35.7% vs 63.7% (HR = 1.63; p = 0.04) and a trend for a higher cumulative incidence of relapse (5-year CIR = 45.7% vs 25.2%, HR = 1.6; p = 0.11). Fusion transcripts status in T-ALL can be robustly identified by RT-MLPA, facilitating risk adapted treatment strategies for high-risk patients. Nature Publishing Group UK 2022-01-26 /pmc/articles/PMC8791998/ /pubmed/35082269 http://dx.doi.org/10.1038/s41408-022-00613-9 Text en © The Author(s) 2022 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
Steimlé, Thomas
Dourthe, Marie-Emilie
Alcantara, Marion
Touzart, Aurore
Simonin, Mathieu
Mondesir, Johanna
Lhermitte, Ludovic
Bond, Jonathan
Graux, Carlos
Grardel, Nathalie
Cayuela, Jean-Michel
Arnoux, Isabelle
Gandemer, Virginie
Balsat, Marie
Vey, Norbert
Macintyre, Elizabeth
Ifrah, Norbert
Dombret, Hervé
Petit, Arnaud
Baruchel, André
Ruminy, Philippe
Boissel, Nicolas
Asnafi, Vahid
Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins
title Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins
title_full Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins
title_fullStr Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins
title_full_unstemmed Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins
title_short Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins
title_sort clinico-biological features of t-cell acute lymphoblastic leukemia with fusion proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791998/
https://www.ncbi.nlm.nih.gov/pubmed/35082269
http://dx.doi.org/10.1038/s41408-022-00613-9
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