Ikaros Deletions among Bulgarian Patients with Acute Lymphoblastic Leukemia/Lymphoma

TL;DR

This study examines the prevalence and impact of IKZF1 gene deletions in Bulgarian patients with acute lymphoblastic leukemia/lymphoma, finding a strong negative effect on survival.

Contribution

The study provides new insights into the prognostic significance of specific IKZF1 deletions in Bulgarian ALL/LBL patients using breakpoint-specific qPCR.

Findings

IKZF1 deletions were found in 19 out of 78 ALL patients, with Δ4–7 being the most common deletion.

Patients with IKZF1 deletions had significantly worse event-free and overall survival compared to those without deletions.

Deletion testing via breakpoint-specific qPCR is proposed as a practical diagnostic tool for risk stratification.

Abstract

The Ikaros zinc finger factor 1 is a transcription factor with a well-known role in B- and T-cell development. The deletions of IKZF1 have an established significance in acute lymphoblastic leukemia, while reports on its prevalence and prognostic significance among ALL subtypes and regions vary. Breakpoint-specific qPCR is a practical method for testing of the most frequent types of IKZF1 deletions, considering there is clustering of the deletion events. The most commonly reported deletions are Δ4–7, Δ4–8, Δ2–7, and Δ2–8, with deletion Δ4–7 being the most common one. We retrospectively administered a breakpoint-specific qPCR design for screening for the most frequent types of IKZF1 deletions to 78 ALL patients that were diagnosed and treated between 2010 and 2022. We observed the products through gel electrophoresis, and we conducted descriptive statistics, EFS, and OS analyses. Our study found 19 patients with IKZF1 deletions, with two subjects manifesting more than one deletion. The prevalence in the different subgroups was as follows: Ph/+/ B-ALL 46%, Ph/−/ B-ALL 30%, T-ALL/LBL 4%. There was a statistically significant difference in EFS of 39 vs. 0% in favor of patients without deletions (p = 0.000), which translated to a difference in OS of 49 vs. 0% (p = 0.001). This difference was preserved in the subgroup of Ph/−/ B-ALL, while there was no significant difference in the Ph/+/ B-ALL. The most frequently observed type of deletion (15 out of 19) was the Δ4–7. There is a strong negative prognostic impact of the IKZF1 deletions at diagnosis in the observed population. IKZF1 deletion testing through breakpoint-specific qPCR is a practical approach in diagnostic testing for this risk factor. IKZF1 deletions may warrant treatment decisions and intensified treatment strategies to overcome the negative prognostic impact.

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