Abstract
Background: In pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the IKZF1 gene deletions is an molecular marker of poor prognosis. We aimed to assess the prognostic effect of different levels of IKZF1 gene deletions in pediatric BCP-ALL.
Procedure: IKZF1 Δ2-8/ALB deletions were quantified using multiplex real-time quantitative PCR (RQ-PCR) in newly diagnosed pediatric BCP-ALL patients between June 2014 and January 2018. Seventy-four patients with IKZF1 deletions of ≥ 0.01% were included. Clinical characteristics, laboratory data, and treatment outcomes were analyzed.
Results: The patients were divided into two groups: IKZF1 deletions of < 1% (Group A) and of ≥ 1% (Group B). Patients in group B had a higher BCR-ABL1 positive rate than those in group A (P = 0.001). The proportions of patients who had an age at onset of ≥10 years old, and white blood cell count ≥ 50×109/L were significantly higher in group B than in group A (P < 0.05). The 3-year overall survival (OS) and 3-year event-free survival (EFS) rates in group B were 79 ± 8.8% and 62.4 ± 9.7%, respectively, which were significantly lower than the 3-year OS (97.7 ± 2.2%, P = 0.022) and 3-year EFS (83.2 ± 5.8%,P = 0.019) in group A. Multivariate analysis revealed that the level of IKZF1 deletions of ≥ 1% and CNSL were independent risk factors of EFS.
Conclusions: Pediatric BCP-ALL patients with high levels of IKZF1 gene deletions have a poorer prognosis than those with low levels.
Introduction
Acute lymphoblastic leukemia (ALL) is the most common childhood malignant cancer, with B-cell precursor ALL (BCP-ALL) accounting for approximately 80% of pediatric ALL cases. The application of molecular biological and cytogenetic techniques has revealed that the translocations t(9;22)/(BCR-ABL1), t(12;21)/(ETV6/RUNX1), t(1;19)/(E2A/PBX1), rearrangements of the MLL gene, and hypodiploid or hypodiploid karyotypes in certain patients with ALL are associated with different prognoses. Patients benefit from risk-adapted treatment protocols. Because of progress in chemotherapy regimens and the development of risk-adapted treatment protocols, the prognosis of ALL in children has significantly improved. The 5-year event-free survival (EFS) rate of pediatric ALL from developed countries can exceed 80%[1], but the remaining patients are still refractory/relapsed with poor prognosis. Therefore, studies are currently focused on identifying high-risk ALL children in an early stage and carrying out the appropriate risk-adapted treatment in order to improve their prognosis.
The IKZF1 gene is located on chromosome 7p12, and encodes the lymphoid transcription protein Ikaros, which plays a key regulatory role in lymphopoiesis [2]. The deletion or mutation of IKZF1 gene are the hallmark of both BCR-ABL1 positive ALL and Ph-like ALL patients. In the most cases, IKZF1 gene deletion has been recognized as a poor prognostic factor in pediatric ALL [3]. Most data on IKZF1 deletions in pediatric ALL have been obtained through multiplex ligation probe-dependent amplification (MLPA) analyses, single nucleotide polymorphism (SNP) arrays, or polymerase chain reaction (PCR) assays, which cannot be used to detect minimal residual disease (MRD) in ALL. Recently, the levels of the IKZF1 Δ2-8/albumin (ALB) gene deletion have been detected using a real-time quantitative polymerase chain reaction (RQ-PCR) approach and used to monitor MRD in ALL. In this study, a quantitative analysis of IKZF1 gene deletion was conducted in pediatric patients with BCP-ALL to explore the relationship between different levels of IKZF1 gene deletions and prognosis.