Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug;40(3):430-441.
doi: 10.1002/hon.2973. Epub 2022 Feb 14.

Prognostic significance of IKZF1 deletions and IKZF1plus profile in children with B-cell precursor acute lymphoblastic leukemia treated according to the ALL-IC BFM 2009 protocol

Marcin Braun  1   2 , Agata Pastorczak  2 , Łukasz Sędek  3 , Joanna Taha  2 , Joanna Madzio  2 , Izabela Jatczak-Pawlik  2 , Kamila Wypyszczak  2 , Michał Matysiak  4 , Katarzyna Derwich  5 , Monika Lejman  6 , Bernarda Kazanowska  7 , Tomasz Szczepański  3 , Jerzy R Kowalczyk  8 , Wojciech Mlynarski  2 ; Polish Pediatric Leukemia/Lymphoma Study Group
Affiliations

Prognostic significance of IKZF1 deletions and IKZF1plus profile in children with B-cell precursor acute lymphoblastic leukemia treated according to the ALL-IC BFM 2009 protocol

Marcin Braun et al. Hematol Oncol. 2022 Aug.

Abstract

The strongest predictors of outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are minimal residual disease (MRD) and specific molecular abnormalities. One unfavorable prognostic factor is the presence of IKZF1 gene aberrations, particularly when co-occurring with high MRD level at the end of induction treatment. The present study determines the predictive value of a recently-defined IKZF1-plus (IKZF1plus ) microdeletion profile in 373 children with BCP-ALL treated according to the ALL-intercontinental Berlin-Frankfurt-Munster protocol 2009 protocol. IKZF1-wild type (IKZF1wt ) patients demonstrated lower leukemic burden parameters than those carrying IKZF1 deletion (IKZF1del [n = 26, 7.0%]) or IKZF1plus pattern (n = 34, 9.1%): (i) median blast percentage at diagnosis (78.0% vs. 86.9% vs. 86.0%; p = 0.021); (ii) median MRD level at day 15 of induction protocol (0.3% vs. 2.1% vs. 0.8%; p = 0.011); (iii) poor steroid response (7.6% vs. 26.5% vs. 12.5%; p = 0.010). Minimal residual disease level at day 33 (MRD33) exceeding 10-4 was more frequently observed in both the IKZF1del and IKZF1plus subgroups than in IKZF1wt patients (n = 9 [36.0%] vs. n = 13 [41.9%] vs. n = 70 [24.0%], p = 0.051). IKZF1plus individuals showed a tendency for a lower MRD reduction between day 15 and 33 compared to IKZF1del patients (p = 0.124). IKZF1del and IKZF1plus patients showed decreased relapse-free survival (HR [95%CI] for IKZF1wt as reference = 2.72 [1.21-6.11] and 2.00 [0.87-4.49], respectively, p = 0.023). Both genetic markers including IKZF1del and IKZF1plus microdeletion profile provide additional predictive value of treatment outcome in childhood BCP-ALL and may contribute to more efficient patient stratification; the same is true in MRD guided protocols, which are based on flow cytometric measurements on day 15 of induction protocol.

Keywords: IKZF1; IKZF1plus; microdeletions; minimal residual disease; pediatric B-cell acute lymphoblastic leukemia.

PubMed Disclaimer

References

REFERENCES

    1. Malard F, Mohty M. Acute lymphoblastic leukaemia. Lancet. 2020;395(10230):1146-1162. https://doi.org/10.1016/s0140-6736(19)33018-1
    1. Nguyen K, Devidas M, Cheng SC, et al. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008;22(12):2142-2150. https://doi.org/10.1038/leu.2008.251
    1. Basso G, Veltroni M, Valsecchi MG, et al. Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol. 2009;27(31):5168-5174. https://doi.org/10.1200/jco.2008.20.8934
    1. Kruse A, Abdel-Azim N, Kim HN, et al. Minimal residual disease detection in acute lymphoblastic leukemia. Int J Mol Sci. 2020;5(3):21. https://doi.org/10.3390/ijms21031054
    1. Zawitkowska J, Lejman M, Romiszewski M, et al. Results of two consecutive treatment protocols in Polish children with acute lymphoblastic leukemia. Sci Rep. 2020;10(1):20168. https://doi.org/10.1038/s41598-020-75860-6

MeSH terms

Substances