Your browser doesn't support javascript.
loading
Integrative genomic analysis of childhood acute lymphoblastic leukaemia lacking a genetic biomarker in the UKALL2003 clinical trial.
Schwab, Claire; Cranston, Ruth E; Ryan, Sarra L; Butler, Ellie; Winterman, Emily; Hawking, Zoe; Bashton, Matthew; Enshaei, Amir; Russell, Lisa J; Kingsbury, Zoya; Peden, John F; Barretta, Emilio; Murray, James; Gibson, Jude; Hinchliffe, Andrew C; Bain, Robert; Vora, Ajay; Bentley, David R; Ross, Mark T; Moorman, Anthony V; Harrison, Christine J.
Afiliação
  • Schwab C; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Cranston RE; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Ryan SL; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Butler E; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Winterman E; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Hawking Z; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Bashton M; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Enshaei A; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Russell LJ; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Kingsbury Z; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK.
  • Peden JF; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK.
  • Barretta E; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Murray J; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Gibson J; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Hinchliffe AC; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Bain R; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Vora A; Department of Haematology, Great Ormond Street Hospital, London, UK.
  • Bentley DR; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK.
  • Ross MT; Illumina Cambridge Ltd., Granta Park, Great Abington, Cambridge, UK.
  • Moorman AV; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK.
  • Harrison CJ; Leukaemia Research Cytogenetics Group, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle upon Tyne, UK. christine.harrison@newcastle.ac.uk.
Leukemia ; 37(3): 529-538, 2023 03.
Article em En | MEDLINE | ID: mdl-36550215
Incorporating genetics into risk-stratification for treatment of childhood B-progenitor acute lymphoblastic leukaemia (B-ALL) has contributed significantly to improved survival. In about 30% B-ALL (B-other-ALL) without well-established chromosomal changes, new genetic subtypes have recently emerged, yet their true prognostic relevance largely remains unclear. We integrated next generation sequencing (NGS): whole genome sequencing (WGS) (n = 157) and bespoke targeted NGS (t-NGS) (n = 175) (overlap n = 36), with existing genetic annotation in a representative cohort of 351 B-other-ALL patients from the childhood ALL trail, UKALL2003. PAX5alt was most frequently observed (n = 91), whereas PAX5 P80R mutations (n = 11) defined a distinct PAX5 subtype. DUX4-r subtype (n = 80) was defined by DUX4 rearrangements and/or ERG deletions. These patients had a low relapse rate and excellent survival. ETV6::RUNX1-like subtype (n = 21) was characterised by multiple abnormalities of ETV6 and IKZF1, with no reported relapses or deaths, indicating their excellent prognosis in this trial. An inferior outcome for patients with ABL-class fusions (n = 25) was confirmed. Integration of NGS into genomic profiling of B-other-ALL within a single childhood ALL trial, UKALL2003, has shown the added clinical value of NGS-based approaches, through improved accuracy in detection and classification into the range of risk stratifying genetic subtypes, while validating their prognostic significance.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras B / Leucemia-Linfoma Linfoblástico de Células Precursoras Limite: Child / Humans Idioma: En Revista: Leukemia Assunto da revista: HEMATOLOGIA / NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras B / Leucemia-Linfoma Linfoblástico de Células Precursoras Limite: Child / Humans Idioma: En Revista: Leukemia Assunto da revista: HEMATOLOGIA / NEOPLASIAS Ano de publicação: 2023 Tipo de documento: Article