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The clinical impact of IKZF1 deletions in paediatric B-cell precursor acute lymphoblastic leukaemia is independent of minimal residual disease stratification in Nordic Society for Paediatric Haematology and Oncology treatment protocols used between 1992 and 2013

Författare och institution:
L. Olsson (-); , II Ofverholm (-); U. Noren-Nystrom (-); V. Zachariadis (-); J. Nordlund (-); Helene Sjögren (Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin); I. Golovleva (-); A. Nordgren (-); K. Paulsson (-); M. Heyman (-); G. Barbany (-); B. Johansson (-)
Publicerad i:
British Journal of Haematology, 170 ( 6 ) s. 847-858
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Paediatric B-cell precursor acute lymphoblastic leukaemias (BCP ALL) with IKZF1 deletions (IKZF1) are associated with a poor outcome. However, there are conflicting data as to whether IKZF1 is an independent risk factor if minimal residual disease (MRD) and other copy number alterations also are taken into account. We investigated 334 paediatric BCP ALL, diagnosed 1992-2013 and treated according to Nordic Society for Paediatric Haematology and Oncology ALL protocols, with known IKZF1 status based on either single nucleotide polymorphism array (N=218) or multiplex ligation-dependent probe amplification (N=116) analyses. IKZF1, found in 15%, was associated with inferior 10-year probabilities of event-free (60% vs. 83%; P<0001) and overall survival (pOS; 73% vs. 89%; P=0001). Adjusting for known risk factors, including white blood cell (WBC) count and MRD, IKZF1 was the strongest independent factor for relapse and death. IKZF1 was present in 27% of cases with non-informative cytogenetics (BCP-other') and a poor 10-year pOS was particularly pronounced in this group (58% vs. 90%; P<0001). Importantly, neither MRD nor WBC count predicted events in the IKZF1-positive cases. Co-occurrence of pseudoautosomal region 1 (PAR1) deletions in Xp22.33/Yp11.32 (P2RY8-CRLF2) and IKZF1 increased the risk of relapse (75% vs. 30% for cases with only IKZF1; P=0045), indicating that BCP-other ALL with both P2RY8-CRLF2 and IKZF1 constitutes a particularly high-risk group.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
paediatric B-cell precursor acute lymphoblastic leukaemia, IKZF1 deletion, P2RY8-CRLF2, minimal, FLOW-CYTOMETRY, GENE DELETIONS, POOR-PROGNOSIS, ERG DELETION, CHILDHOOD, RISK, CRLF2, CHILDREN, IKAROS, REVEALS, Hematology
Postens nummer:
Posten skapad:
2015-10-05 14:07
Posten ändrad:
2015-11-25 16:13

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