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Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study

Chromosomal abnormalities are established prognostic markers in adult ALL. We assessed the prognostic impact of established chromosomal abnormalities and key copy number alterations (CNA) among 652 patients with B-cell precursor ALL treated on a modern MRD driven protocol. Patients with KMT2A-AFF1,...

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Autores principales: Moorman, Anthony V., Barretta, Emilio, Butler, Ellie R., Ward, Eleanor J., Twentyman, Katie, Kirkwood, Amy A., Enshaei, Amir, Schwab, Claire, Creasey, Tom, Leongamornlert, Daniel, Papaemmanuil, Elli, Patrick, Pip, Clifton-Hadley, Laura, Patel, Bela, Menne, Tobias, McMillan, Andrew K., Harrison, Christine J., Rowntree, Clare J., Marks, David I., Fielding, Adele K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885405/
https://www.ncbi.nlm.nih.gov/pubmed/34657128
http://dx.doi.org/10.1038/s41375-021-01448-2
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author Moorman, Anthony V.
Barretta, Emilio
Butler, Ellie R.
Ward, Eleanor J.
Twentyman, Katie
Kirkwood, Amy A.
Enshaei, Amir
Schwab, Claire
Creasey, Tom
Leongamornlert, Daniel
Papaemmanuil, Elli
Patrick, Pip
Clifton-Hadley, Laura
Patel, Bela
Menne, Tobias
McMillan, Andrew K.
Harrison, Christine J.
Rowntree, Clare J.
Marks, David I.
Fielding, Adele K.
author_facet Moorman, Anthony V.
Barretta, Emilio
Butler, Ellie R.
Ward, Eleanor J.
Twentyman, Katie
Kirkwood, Amy A.
Enshaei, Amir
Schwab, Claire
Creasey, Tom
Leongamornlert, Daniel
Papaemmanuil, Elli
Patrick, Pip
Clifton-Hadley, Laura
Patel, Bela
Menne, Tobias
McMillan, Andrew K.
Harrison, Christine J.
Rowntree, Clare J.
Marks, David I.
Fielding, Adele K.
author_sort Moorman, Anthony V.
collection PubMed
description Chromosomal abnormalities are established prognostic markers in adult ALL. We assessed the prognostic impact of established chromosomal abnormalities and key copy number alterations (CNA) among 652 patients with B-cell precursor ALL treated on a modern MRD driven protocol. Patients with KMT2A-AFF1, complex karyotype (CK) and low hypodiploidy/near-triploidy (HoTr) had high relapse rates 50%, 60% & 53% and correspondingly poor survival. Patients with BCR-ABL1 had an outcome similar to other patients. JAK-STAT abnormalities (CRLF2, JAK2) occurred in 6% patients and were associated with a high relapse rate (56%). Patients with ABL-class fusions were rare (1%). A small group of patients with ZNF384 fusions (n = 12) had very good survival. CNA affecting IKZF1, CDKN2A/B, PAX5, BTG1, ETV6, EBF1, RB1 and PAR1 were assessed in 436 patients. None of the individual deletions or profiles were associated with survival, either in the cohort overall or within key subgroups. Collectively these data indicate that primary genetic abnormalities are stronger prognostic markers than secondary deletions. We propose a revised UKALL genetic risk classification based on key established chromosomal abnormalities: (1) very high risk: CK, HoTr or JAK-STAT abnormalities; (2) high risk: KMT2A fusions; (3) Tyrosine kinase activating: BCR-ABL1 and ABL-class fusions; (4) standard risk: all other patients.
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spelling pubmed-88854052022-03-17 Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study Moorman, Anthony V. Barretta, Emilio Butler, Ellie R. Ward, Eleanor J. Twentyman, Katie Kirkwood, Amy A. Enshaei, Amir Schwab, Claire Creasey, Tom Leongamornlert, Daniel Papaemmanuil, Elli Patrick, Pip Clifton-Hadley, Laura Patel, Bela Menne, Tobias McMillan, Andrew K. Harrison, Christine J. Rowntree, Clare J. Marks, David I. Fielding, Adele K. Leukemia Article Chromosomal abnormalities are established prognostic markers in adult ALL. We assessed the prognostic impact of established chromosomal abnormalities and key copy number alterations (CNA) among 652 patients with B-cell precursor ALL treated on a modern MRD driven protocol. Patients with KMT2A-AFF1, complex karyotype (CK) and low hypodiploidy/near-triploidy (HoTr) had high relapse rates 50%, 60% & 53% and correspondingly poor survival. Patients with BCR-ABL1 had an outcome similar to other patients. JAK-STAT abnormalities (CRLF2, JAK2) occurred in 6% patients and were associated with a high relapse rate (56%). Patients with ABL-class fusions were rare (1%). A small group of patients with ZNF384 fusions (n = 12) had very good survival. CNA affecting IKZF1, CDKN2A/B, PAX5, BTG1, ETV6, EBF1, RB1 and PAR1 were assessed in 436 patients. None of the individual deletions or profiles were associated with survival, either in the cohort overall or within key subgroups. Collectively these data indicate that primary genetic abnormalities are stronger prognostic markers than secondary deletions. We propose a revised UKALL genetic risk classification based on key established chromosomal abnormalities: (1) very high risk: CK, HoTr or JAK-STAT abnormalities; (2) high risk: KMT2A fusions; (3) Tyrosine kinase activating: BCR-ABL1 and ABL-class fusions; (4) standard risk: all other patients. Nature Publishing Group UK 2021-10-16 2022 /pmc/articles/PMC8885405/ /pubmed/34657128 http://dx.doi.org/10.1038/s41375-021-01448-2 Text en © The Author(s) 2021 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
Moorman, Anthony V.
Barretta, Emilio
Butler, Ellie R.
Ward, Eleanor J.
Twentyman, Katie
Kirkwood, Amy A.
Enshaei, Amir
Schwab, Claire
Creasey, Tom
Leongamornlert, Daniel
Papaemmanuil, Elli
Patrick, Pip
Clifton-Hadley, Laura
Patel, Bela
Menne, Tobias
McMillan, Andrew K.
Harrison, Christine J.
Rowntree, Clare J.
Marks, David I.
Fielding, Adele K.
Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study
title Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study
title_full Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study
title_fullStr Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study
title_full_unstemmed Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study
title_short Prognostic impact of chromosomal abnormalities and copy number alterations in adult B-cell precursor acute lymphoblastic leukaemia: a UKALL14 study
title_sort prognostic impact of chromosomal abnormalities and copy number alterations in adult b-cell precursor acute lymphoblastic leukaemia: a ukall14 study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8885405/
https://www.ncbi.nlm.nih.gov/pubmed/34657128
http://dx.doi.org/10.1038/s41375-021-01448-2
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