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The prognostic impact of IKZF1 deletions and UKALL genetic classifiers in paediatric B-cell precursor acute lymphoblastic leukaemia treated according to NOPHO 2008 protocols.
Öfverholm, Ingegerd; Rezayee, Fatemah; Heyman, Mats; Harila, Arja; Arvidsson, Linda; Schmiegelow, Kjeld; Norén-Nyström, Ulrika; Barbany, Gisela.
Afiliación
  • Öfverholm I; Department of Molecular Medicine and Surgery and Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
  • Rezayee F; Department of Molecular Medicine and Surgery and Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
  • Heyman M; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
  • Harila A; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
  • Arvidsson L; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Schmiegelow K; Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
  • Norén-Nyström U; Faculty of Medicine, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
  • Barbany G; Department of Clinical Sciences, Paediatrics, Umeå University, Umeå, Sweden.
Br J Haematol ; 202(2): 384-392, 2023 07.
Article en En | MEDLINE | ID: mdl-37156607
We investigated 390 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients treated according to NOPHO ALL 2008, regarding copy number alterations (CNA) of eight loci associated with adverse prognosis, including IKZF1. The impact on outcome was investigated for each locus individually, combined as CNA profiles and together with cytogenetic information. The presence of IKZF1 deletion or a poor-risk CNA profile was associated with poor outcome in the whole cohort. In the standard-risk group, IKZF1-deleted cases had an inferior probability of relapse-free survival (pRFS) (p ≤ 0.001) and overall survival (pOS) (p ≤ 0.001). Additionally, among B-other patients, IKZF1 deletion correlated with poor pRFS (60% vs. 90%) and pOS (65% vs. 89%). Both IKZF1 deletion and a poor-risk CNA profile were independent factors for relapse and death in multivariable analyses adjusting for known risk factors including measurable residual disease. Our data indicate that BCP-ALL patients with high-risk CNA or IKZF1 deletion have worse prognosis despite otherwise low-risk features. Conversely, patients with both a good CNA and cytogenetic profile had a superior relapse-free (p ≤ 0.001) and overall survival (p ≤ 0.001) in the cohort, across all risk groups. Taken together, our findings highlight the potential of CNA assessment to refine stratification in ALL.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras B / Recurrencia Local de Neoplasia Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Humans Idioma: En Revista: Br J Haematol Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia-Linfoma Linfoblástico de Células Precursoras B / Recurrencia Local de Neoplasia Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Child / Humans Idioma: En Revista: Br J Haematol Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido