Prevalence and prognostic significance of IKZF1 deletion in paediatric acute lymphoblastic leukemia: A systematic review and meta-analysis.
Shyam SrinivasanSubramaniam RamanathanShathish KumarSrinivasan PeyamVenkatraman RadhakrishnanPublished in: Annals of hematology (2023)
IKZF1 (IKAROS family Zinc Finger 1) alteration is an essential regulator of both T- and B-cell lineage specification with leukemogenic potential. IKZF1 deletion have been described in childhood acute lymphoblastic leukemia (ALL) with varying prevalence often influenced by underlying cytogenetics and also shown to have diverse prognostic significance. We aimed to evaluate the prevalence and prognostic significance of IKZF1 deletion among childhood ALL. Electronic databases of MEDLINE, EMBASE and SCOPUS were searched and 32 studies found eligible. Estimated prevalence of IKZF1 deletion among BCR::ABL1 negative and BCR::ABL1 positive ALL patients was 14% (95%CI:13-16%, I 2 = 79%; 26 studies) and 63% (95%CI:59-68% I 2 = 42%; 10 studies) respectively. Most common site of IKZF1 deletion was whole chromosome (exon1-8) deletion in 32.3% (95%CI: 23.8-40.7%) followed by exon 4-7 deletion in 28.6% (95%CI: 19.7-37.5%). A positive minimal residual disease at the end of induction was more common among patients with IKZF1 deletion, odds ratio: 3.09 (95%CI:2.3-4.16, I 2 = 54%; 15 studies). Event-free survival and overall survival were significantly worse for IKZF1 deletion, hazard ratio (HR): 2.10 (95%CI:1.90-2.32, I 2 = 28%; 31 studies) and HR: 2.38 (95%CI:1.93-2.93, I 2 = 40; 15 studies) respectively. In summary, the current meta-analysis highlights the frequency of IKZF1 deletion and its negative impact on survival in childhood ALL. Further studies exploring the influence of IKZF1 deletion in the presence of classical cytogenetic and other copy number alterations would further help in characterising its prognostic role.
Keyphrases
- acute lymphoblastic leukemia
- allogeneic hematopoietic stem cell transplantation
- case control
- copy number
- risk factors
- free survival
- systematic review
- end stage renal disease
- tyrosine kinase
- randomized controlled trial
- climate change
- ejection fraction
- emergency department
- chronic kidney disease
- early life
- chronic myeloid leukemia
- newly diagnosed
- deep learning
- patient reported outcomes