CLINICAL AND MOLECULAR STUDY OF THE RS3824662 POLYMORPHISM IN

@article{santos2026clinical,
  title = {{CLINICAL AND MOLECULAR STUDY OF THE RS3824662 POLYMORPHISM IN}},
  author = {Rafael Lima SANTOS and Thamyris Figueiredo AMARAL and Marianna Dantas VILLARES and Caroline Barbieri BLUNCK and Thais Ferraz AGUIAR and Irtis Pessanha OLIVEIRA and Renata Baldi PESSANHA and Marcia Trindade SCHRAMM and Jordana Santos Ramires ARAGÃO and Maura Valério IKOMA and Maria Vanuza ROSA and Mecneide Mendes LINS and Patricia HORN and Renata LYRIO and Cristina WIGGERS and Gildene Alves da COSTA and Patricia Carla LIMA and Bruno Alves LOPES and Mariana EMERENCIANO and Thayana da Conceição BARBOSA},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107571},
  url = {https://doi.org/10.1016/j.htct.2026.107571},
  note = {CC BY},
}

TY  - JOUR
TI  - CLINICAL AND MOLECULAR STUDY OF THE RS3824662 POLYMORPHISM IN
AU  - Rafael Lima SANTOS
AU  - Thamyris Figueiredo AMARAL
AU  - Marianna Dantas VILLARES
AU  - Caroline Barbieri BLUNCK
AU  - Thais Ferraz AGUIAR
AU  - Irtis Pessanha OLIVEIRA
AU  - Renata Baldi PESSANHA
AU  - Marcia Trindade SCHRAMM
AU  - Jordana Santos Ramires ARAGÃO
AU  - Maura Valério IKOMA
AU  - Maria Vanuza ROSA
AU  - Mecneide Mendes LINS
AU  - Patricia HORN
AU  - Renata LYRIO
AU  - Cristina WIGGERS
AU  - Gildene Alves da COSTA
AU  - Patricia Carla LIMA
AU  - Bruno Alves LOPES
AU  - Mariana EMERENCIANO
AU  - Thayana da Conceição BARBOSA
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107571
UR  - https://doi.org/10.1016/j.htct.2026.107571
AB  - Background: The rs3824662 single nucleotide polymorphism (SNP) in the GATA3 gene is a known risk factor for developing B-cell precursor acute lymphoblastic leukemia (B-ALL). The high prevalence of adverse genetic alterations, together with the absence of specific treatment protocols for adolescents and young adults (AYA), has negatively impacted the prognosis in this age group. Moreover, studies evaluating this SNP in GATA3 among AYA patients are scarce in the literature. Aim: In this context, this study aims to evaluate the clinical and molecular characteristics related to the rs3824662 polymorphism in AYA B-ALL. Method: A total of 104 samples from AYA patients (15 to 39 years) diagnosed with B-ALL between 2018 and 2025 were included, in accordance with World Health Organization (WHO) criteria. Samples were obtained from different cancer treatment centers in Brazil. DNA was extracted using the DNA Mini Blood kit, following the manufacturer's protocol. The rs3824662 polymorphism was genotyped using the TaqMan assay (C_27522049_10), and the genotypes obtained were validated by direct sequencing. The BCR::ABL1-like subtype was characterized by the presence of rearrangements involving the PDGFRB, CRLF2, JAK2, ABL1, ABL2, IGH, and/or CSF1R genes, detected by FISH. The rs3824662 polymorphism was correlated with previously characterized clinical and molecular variables, including primary and additional alterations identified by qPCR and MLPA P335-C1 kit. Statistical analyses were performed using RStudio software. Associations between rs3824662 polymorphism genotypes and categorical clinical and molecular variables were assessed using the chi-square test or Fisher's exact test. Overall survival (OS) was analyzed using the survival and survminer packages. This project was approved by the Research Ethics Committee of the National Cancer Institute (INCA), under approval number (#87793418.0.0000.5274). Results: Among the patients analyzed, the median age was 19.5 years, 60% presented low white blood cell (WBC) counts, and the most frequent molecular subgroups were B-other (36.1%) and BCR::ABL1 (30.1%). GATA3 genotypes were distributed as 40.4% wild-type (CC), 41.3% heterozygous (CA), and 18.3% mutant homozygous (AA). Low WBC predominated among heterozygous patients (66.7%, P=0.004). BCR::ABL1 and B-other subtypes were the most frequent in patients carrying the risk allele (P<0.05). BCR::ABL1-like subtype was more prevalent among mutant allele carriers (70% vs 28.6%), who also showed frequent deletions in IKZF1, CDKN2A/B, and PAX5, but no deletions in the PAR1 region were observed. Although OS did not differ significantly across genotypes, independently of the genetic model tested, there was a trend toward poorer outcomes in AA patients. Curiously, the predominance of low WBC count in CA patients classifying these patients as good responders to treatment. Conclusion: Our study reinforces the role of the rs3824662 polymorphism in GATA3 in AYA B-ALL, showing a high prevalence of the risk allele (A) in this cohort. The most prevalent subtypes were BCR::ABL1- like, BCR::ABL1, and B-other, regardless of the GATA3 SNP genotype, reflecting the cohort’s genomic heterogeneity. The apparently favorable outcome in AC patients likely results from other prognostic factors, underscoring the need for larger cohorts to confirm the impact of this genotype on survival.
SN  - 2531-1379
SN  - 2531-1387
ER  -