Cancers (Jul 2022)

Impact of <i>IKZF1</i> Deletions in the Prognosis of Childhood Acute Lymphoblastic Leukemia in Argentina

  • María Sara Felice,
  • Patricia Laura Rubio,
  • Jorge Digiorge,
  • Mariángeles Barreda Frank,
  • Celeste Sabrina Martínez,
  • Myriam Ruth Guitter,
  • Elisa Olga Sajaroff,
  • Cristian Germán Sánchez La Rosa,
  • Carla Luciana Pennella,
  • Luisina Belén Peruzzo,
  • María Alejandra Deu,
  • Elizabeth Melania Alfaro,
  • María Constanza Guardia,
  • Gladys Gutierrez,
  • María Angelica Fernández Barbieri,
  • Ezequiel Recondo,
  • María Soledad Vides Herrera,
  • Vanina Livio,
  • Constanza Arnaiz,
  • Carolina Romero,
  • Cristina Noemi Alonso,
  • Jorge Gabriel Rossi

DOI
https://doi.org/10.3390/cancers14133283
Journal volume & issue
Vol. 14, no. 13
p. 3283

Abstract

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An association of deletions in the IKZF1 gene (IKZF1del) with poor prognosis in acute lymphoblastic leukemia (ALL) has been demonstrated. Additional deletions in other genes (IKZF1plus) define different IKZF1del subsets. We analyzed the influence of IKZF1del and/or IKZF1plus in the survival of children with ALL. From October 2009 to July 2021, 1055 bone marrow samples from patients with ALL were processed by Multiplex ligation-dependent probe amplification (MLPA). Of them, 28 patients died during induction and 4 were lost-in-follow-up, resulting in an eligible 1023 cases. All patients were treated according to ALLIC-BFM-2009-protocol. Patients were classified into three subsets: IKZF1not-deleted (IKZFF1not-del), IKZF1deleted (IKZF1del) and IKZF1del plus deletion of PAX5, CDKN2A, CDKN2B and/or alterations in CRLF2 with ERG-not-deleted (IKZF1plus). The LFSp and SE were calculated with the Kaplan–Meier calculation and compared with a log-rank test. From the 1023 eligible patients, 835 (81.6%) were defined as IKZF1not-del, 94 (9.2%) as IKZF1del and 94 (9.2%) as IKZF1plus. Of them, 100 (9.8%) corresponded to Standard-Risk (SRG), 629 (61.5%) to Intermediate-Risk (IRG) and 294 (28.7%) to High-Risk (HRG) groups. LFSp(SE) was 7 5(2)% for IKZF1not-del, 51 (6)% for IKZF1del and 48 (6)% for IKZF1plus (p-value p-value = ns); in IRG, 77 (2)% IKZF1not-del, 61 (10)% IKZF1del and 54 (7)% IKZF1plus (p-value = 0.0005) and in HRG, 61 (4)% IKZF1not-del, 38 (8)% IKZF1del and 35 (9)% IKZF1plus (p-value = 0.0102). The IKZF1 status defines a population of patients with a poor outcome, mainly in IRG. No differences were observed between IKZF1del versus IKZF1plus. MLPA studies should be incorporated into the risk-group stratification of pediatric ALL.

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