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.