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Objective: Acute Lymphoblastic Leukemia (ALL) is classified according to its genetic abnormalities, which are associated with the clinical and biological characteristics of the disease. The detection of gene fusions assists in diagnosis, risk stratification, and targeted therapy. This study aims to evaluate the status of gene fusions in pediatric ALL patients from the Brazilian Amazon and their association with known hematological parameters. Materials and methods: The research was approved by the ethics committee under number 4.040.805 and included a total of 160 patients diagnosed with ALL at the Octávio Lobo Children's Oncology Hospital during the period from 2017 to 2023. Clinical data (leukometry, platelets, and hemoglobin) and epidemiological data (gender and age) were collected from the hospital's database system. For the analysis of gene fusions, c-DNA was obtained for the detection of molecular biomarkers by PCR using specific primers. Agarose gel electrophoresis was performed to visualize the PCR products. Finally, Sanger Sequencing was carried out to confirm the PCR results. For qualitative variables, descriptive statistics were used, determining absolute and percentage frequencies. For quantitative variables, median and standard deviation values were calculated according to the variables under study. The Kruskal-Wallis test was performed to test the association of the presence of one of the gene fusions (BCR::ABL, TCF3::PBX1, KMT2A::AFF1, ETV6::RUNX1 and SIL::TAL) with the clinical data, adopting a p-value ≤ 0.05 as significant. Statistical analyses were performed using RStudio 12.1 software. Results: Regarding gene fusions, 21% of patients had the TCF3::PBX1 fusion, 19% ETV6::RUNX1, 11% BCR::ABL, 3% KMT2A::AFF1, 2% SIL::TAL, and 44% had none of the studied fusions. 61% of the patients were male and 39% female, with a median age of 6 years. Regarding clinical data, the patients had a median white blood cell (WBC) count of 13,150/mm3; a median platelet count of 36,000/mm3; and a median hemoglobin level of 8 g/dL. The Kruskal-Wallis test revealed a significant statistical difference between gene fusions and white blood cell count (p-value = 0.0024), and Dunn's post-test showed that in TCF3::PBX1, the WBC count is significantly higher mainly compared to ETV6::RUNX1 (p-value = 0.007). Discussion: Studies have reported ETV6::RUNX1 as the most frequent fusion, but this work found TCF3::PBX1 as the most frequent find, which may be explained by the highly mixed population of the Amazon, supporting the existence of ethnic differences. Other studies found significant statistical differences in white blood cell count between the TCF3::PBX1 fusion and others, which corroborates the findings of this study, indicating that this molecular biomarker has a poor prognosis and is characterized by a white blood cell count above 50,000/mm3, which was found in about 35% of the patients in this study. Conclusion: In the study, the frequency of the TCF3::PBX1 fusion was observed to be relatively higher than what is reported in the literature. The TCF3::PBX1 fusion leads to the activation of genes encoding proteins with malignant potential, and that the fusion showed a statistical difference between groups regarding white blood cell count, which is used as a risk classification according to the National Cancer Institute.

Objetivo: Demonstrar o ciclo de melhoria contínua, aplicado ao uso das auditorias transfusionais na hemovilância, através da implantação de uma ferramenta web, neste processo, deixando de realizá-lo manualmente para fazê-lo de forma digital. Materiais e métodos: : Processo sistemático otimizado digitalmente, adaptado para um formulário na plataforma web chamado de google formulários, onde são incluidos 12 itens avaliáveis. Realizada aplicação diária para obtenção da coleta de dados do processo de hemovigilância relativo a cada transfusão de produtos sanguíneos, avaliando desde a indicação transfusional, solicitação do hemocomponente, coleta de amostras de sangue do paciente, realização dos exames imunohematológicos, liberação do hemocomponente, entrega no setor assistencial, e o ato transfusional. Esta nova tecnologia digital foi avaliada durante 12 meses, considerando os ítens: eficácia, rapidez, economia e confiabilidade dos dados. Resultados: Após aplicação diária sistemática desta metodologia web durante 12 meses, consegui-se otimizar o tempo de coleta de dados que era em média de 36 minutos utilizando-se a forma manual, ( ficha impressa ) para 14 minutos na modalidade digital, reduzindo este tempo em 22 minutos, por auditoria transfusional. Com esta otimização consegui-se aumentar a coleta de dados para 100% das transfusões realizadas no Hospital Oncológico Infantil Octávio Lobo. Economia foi também observada no consumo de papel, resultando no não uso de em média 300 folhas de papel por mês. Outras vantagens também percebidas foram a disponibilidade mais rápida e fidedígna da informação em gráficos e tabelas para apresentações e análises que geram planos de ação. Discussão: O Hospital Oncológico Infantil Octávio Lobo é a única entidade pública a atender pacientes pediátricos com câncer no Estado do Pará, tendo um grande número de atendimentos para este perfil de pacientes, que habitualmente precisam de transfusões sanguíneas para dar continuidade a seus tratamentos quimioterápicos, consequentemente, levando a uma necessidade de processos hemoterápicos seguros, além de protocolos de hemovigilância cada vez mais complexos, sendo portanto um desafio. Este fato nos levou a procurar formas de otimizar os processos tendo em vista sempre a qualidade e segurança do atendimento. O formulário manual da auditoria transfusional, resultava em um gasto alto em papel e tempo, e portanto não realizava-se auditoria transfusional em 100% das transfusões, tendo o uso desta tecnologia corroborado para a melhoria do processo. Conclusão: A utilização da modalidade digital de coleta de dados para auditoria transfusional resultou em otimização de tempo, recursos em papel, e melhores formas de estratificação de resultados para análises e planos de ação da equipe da Agência Transfusional do Hospital Oncológico Infantil Octavio Lobo.

Objective: This study compares the dose intensity of induction regimens by evaluating outcomes such as early deaths, death in the first remission, and survival. The results of this study will contribute to the development of therapeutic protocols with a reasonable balance in the intensity of induction, allowing remission to be achieved with less toxicity, adapting and establishing the treatment for acute childhood myeloid leukemia in developing countries. Methods: Pubmed and Scopus were used for systematic searches performed in January 2021. Descriptors involving specific or synonymic words such as Acute myeloid leukemia, pediatric, induction, and dose-intensity combined with Boolean operators AND and OR were used, without limits of time-frame or language. All relevant studies were read in full, and the data extraction was performed for those that fulfilled the inclusion criteria (patients aged between 0–21 years old, diagnosed with AML, describing results of induction regimens where one of the groups – intervention or comparison –included different dosing for the same chemotherapy drug). Were excluded the studies publishing exclusively Down's Syndrome patients and acute promyelocytic leukemia diagnosis, single-arm studies (with no comparator group), and studies where the intervention group had a different chemotherapy regimen than the comparator group. Results: The initial search retrieved 1185 papers. In the second round of screening of the remaining 207 articles, full-text papers were assessed for eligibility. From the nine papers included with dose modification during the induction phase of chemotherapy treatment, six referred to changes on cytarabine (ARA-C), two on idarubicin (IDR), and two on daunorubicin (DNR) (one of these studies simultaneously changed ARA-C and DNR). Results showed no significant difference between standard vs. high doses for CR and death during induction. Relapse rates were higher in the standard-dose than in the high-dose arms (1.44; 95% IC: 1.22–1.69). Despite the higher risk of relapse in the standard-dose group, event-free survival analysis shows no significant difference between the arms of each study. Discussion: The outcome of AML treatment in children and adolescents has improved over the last decades. Overall survival rates are now superior to 70% due to implementing strategies such as intensification of therapy, refinements in supportive care, and more precise risk classification. However, treatment-related deaths are exceptionally high in places with limited resources. Even regimens with standard-dose chemotherapy are associated with life-threatening complications due to profound myelosuppression and organ dysfunction. Establishing the best combination and sequence of treatment components, including hematopoietic stem cell transplantation, remains an unmet need. Conclusion: There is no significant difference between standard vs. high doses of chemotherapy during induction for selected outcomes such as complete remission and event-free survival. Reducing the dose intensity of standard AML remission induction regimens should be investigated in regions with limited resources.

Background: Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system characterized by a clonal expansion of abnormal lymphocyte precursor cells. ALL is the most common form of cancer in children, but despite advances in treatment, it can still be fatal. Ethnic differences influence survival rates, and genomic ancestry plays an important role, especially in mixed-race populations such as Latin America. This study aims to analyze the influence of genomic ancestry on toxicity in children with ALL in the Amazon region., Methods: The study included 171 patients (protocol number 119,649/2012-Ethics Committee) with ALL treated at a pediatric treatment center in Belém do Pará, in the Brazilian Amazon. The patients were submitted to the BFM protocol of induction therapy for ALL. Toxicity was assessed based on laboratory tests and adverse events, classified according to the CTC-NCI guide. Genomic ancestry was determined using autosomal informative markers., Results: The majority of children (94.74%) developed some type of toxicity during treatment, 87.04% of which were severe. Infectious toxicity was the most common, present in 84.8% of cases, 77.24% of which were severe. Amerindian ancestry showed an association with the risk of severe general toxicity and severe infectious toxicity, with a contribution of 35.0% demonstrating a significant increase in risk. In addition, post-induction refractoriness and relapse were also associated with an increased risk of death., Conclusion: This study highlights the influence of Amerindian genomic ancestry on response to therapy and toxicity in children with ALL in the Amazon region. Understanding these associations can contribute to personalizing treatment and improving clinical outcomes., (© 2024. The Author(s).)

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world. Single nucleotide variants (SNVs) in miRNA and genes encoding proteins of the miRNA synthesis complex (SC) may affect the processing of drugs used in the treatment of ALL, resulting in treatment-related toxicities (TRTs). We investigated the role of 25 SNVs in microRNA genes and genes encoding proteins of the miRNA SC, in 77 patients treated for ALL-B from the Brazilian Amazon. The 25 SNVs were investigated using the TaqMan ® OpenArray™ Genotyping System. SNVs rs2292832 ( MIR149 ), rs2043556 ( MIR605 ), and rs10505168 ( MIR2053 ) were associated with an increased risk of developing Neurological Toxicity, while rs2505901 ( MIR938 ) was associated with protection from this toxicity. MIR2053 (rs10505168) and MIR323B (rs56103835) were associated with protection from gastrointestinal toxicity, while DROSHA (rs639174) increased the risk of development. The rs2043556 ( MIR605 ) variant was related to protection from infectious toxicity. SNVs rs12904 ( MIR200C ), rs3746444 ( MIR499A ), and rs10739971 ( MIRLET7A1 ) were associated with a lower risk for severe hematologic toxicity during ALL treatment. These findings reveal the potential for the use of these genetic variants to understand the development of toxicities related to the treatment of ALL in patients from the Brazilian Amazon region.

A number of genomic variants related to native American ancestry may be associated with an increased risk of developing Acute Lymphoblastic Leukemia (ALL), which means that Latin American and hispanic populations from the New World may be relatively susceptible to this disease. However, there has not yet been any comprehensive investigation of the variants associated with susceptibility to ALL in traditional Amerindian populations from Brazilian Amazonia. We investigated the exomes of the 18 principal genes associated with susceptibility to ALL in samples of 64 Amerindians from this region, including cancer-free individuals and patients with ALL. We compared the findings with the data on populations representing five continents available in the 1000 Genomes database. The variation in the allele frequencies found between the different groups was evaluated using Fisher's exact test. The analyses of the exomes of the Brazilian Amerindians identified 125 variants, seven of which were new. The comparison of the allele frequencies between the two Amerindian groups analyzed in the present study (ALL patients vs. cancer-free individuals) identified six variants (rs11515, rs2765997, rs1053454, rs8068981, rs3764342, and rs2304465) that may be associated with susceptibility to ALL. These findings contribute to the identification of genetic variants that represent a potential risk for ALL in Amazonian Amerindian populations and might favor precision oncology measures.

In Brazil, Acute lymphoid leukemia (ALL) is the leading cause of cancer deaths in children and adolescents. Treatment toxicity is one of the reasons for stopping chemotherapy. Amerindian genomic ancestry is an important factor for this event due to fluctuations in frequencies of genetic variants, as in the NUDT15 and SLC22A1 genes, which make up the pharmacokinetic and pharmacodynamic pathways of chemotherapy. This study aimed to investigate possible associations between NUDT15 (rs1272632214) and SLC22A1 (rs202220802) gene polymorphism and genomic ancestry as a risk of treatment toxicities in patients with childhood ALL in the Amazon region of Brazil. The studied population consisted of 51 patients with a recent diagnosis of ALL when experiencing induction therapy relative to the BFM 2009 protocol. Our results evidenced a significant association of risk of severe infectious toxicity for the variant of the SLC22A1 gene (OR: 3.18, p = 0.031). Genetic ancestry analyses demonstrated that patients who had a high contribution of African ancestry had a significant protective effect for the development of toxicity (OR: 0.174; p = 0.010), possibly due to risk effects of the Amerindian contribution. Our results indicate that mixed populations with a high degree of African ancestry have a lower risk of developing general toxicity during induction therapy for ALL. In addition, individuals with the SLC22A1 variant have a higher risk of developing severe infectious toxicity while undergoing the same therapy.

Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, representing about 30-35% of cases. Its etiology is complex and not fully understood. ALL is influenced by genetic variants, and their frequencies (Fq) vary in different ethnic groups, which consequently could influence the epidemiology of this cancer worldwide. The aim of this study was to investigate the correlation between the genetic variants and their impacts on incidence (IC), mortality (MT), and prevalence (PV) rates of ALL in different world populations., Methods: Sixty variants were selected from the literature with Genome Wide Association studies (GWAS). Information regarding allele Fq was selected from the 1000 Genomes platform. Epidemiological data were taken from the Global Burden of disease visualisations (GBD) Compare website. Statistical analyses were calculated in RStudio v.3.5.1 software., Results: Four variants demonstrated significant results in correlations with epidemiological data for ALL. The PAX5 gene variant (rs2297105) had an indirect relationship with PV and IC of ALL, showing that an increased Fq of this variant is related to low rates of both. An increased Fq of rs915172 in EPB4IL2 gene was also correlated with a lower IC of ALL. The rs1048943 of the CYP1A1 gene and the rs3088440 polymorphism of the CDKN2A gene were shown to have a direct proportional relationship with MT rate, showing that an increased Fq of these variants correlates with a worse prognosis worldwide., Conclusion: Our study points out four important variants for understanding the IC, PV, and MT rates for ALL. The ascertainment of these data may help to choose molecular markers to investigate the susceptibility and prognosis of ALL.

Acute Lymphoblastic Leukemia (ALL) is a neoplasm of the hematopoietic system defined as a clonal expansion of an abnormal lymphoid precursor cell. It mostly affects children under five years of age and is the most common tumor to afflict pediatric patients. The expression of the human telomerase gene ( hTERT ) in patients with ALL has been studied as a biomarker and could become a new therapeutic target. We evaluate the role of hTERT gene expression in ALL pediatric patients, through quantitative real-time PCR technique, and the possible correlation between hTERT expression and clinical variables: gender, age, white blood cells (WBC), gene fusions, and immunophenotyping. The analysis between healthy controls and ALL patients ( N = 244) was statistically significant ( p < 0.001), demonstrating hTERT overexpression in these patients. In comparison with the usual set of clinical variables, the data were not statistically significant ( p > 0.05), indicating that hTERT is equally overexpressed among patients regardless of gender, age, gene fusions, and immunophenotyping. Moreover, patients who presented a higher hTERT expression level had a significant ( p < 0.0001) lower overall survival rate. In summary, hTERT expression emerges as an important molecular pathway in leukemogenesis regardless patient's clinical variables, thus, the data here presented pointed it as a valuable biomarker in pediatric acute lymphoblastic leukemia and a promising target for new therapeutic and prognostic measures.

Objective: To assess the performance of Pediatric Risk of Mortality (PRISM) III and Pediatric Index of Mortality (PIM) 2 scores in the pediatric intensive care unit., Methods: A retrospective cohort study. Data were retrospectively collected from medical records of all patients admitted to the pediatric intensive care unit of a cancer hospital from January 2017 to June 2018., Results: The mean PRISM III score was 15, and PIM 2, 24%. From the 338 studied patients, 62 (18.34%) died. The PRISM III estimated mortality was 79.52 patients (23.52%) and for PIM 2 80.19 patients (23.72%), corresponding to a standardized mortality ratio (95% confidence interval: 0.78 for PRISM II and 0.77 for PIM 2). The Hosmer-Lemeshow chi-square test was 11.56, 8df, 0.975 for PRISM II and 0.48, 8df, p = 0.999 for PIM 2. The area under the Receiver Operating Characteristic curve was 0.71 for PRISM III and 0.76 for PIM 2., Conclusion: Both scores overestimated mortality and have shown a regular ability to discriminate between survivors and non-survivors. Models should be developed to quantify the severity of cancer pediatric patients in Pediatric Intensive Care Units and to predict the mortality risk accounting for their peculiarities.

Acute Lymphoblastic Leukemia (ALL) is the most common type of cancer in children. Polymorphisms that alter the normal function of the microRNAs involved in the development of ALL have been widely investigated, although published data on these polymorphisms in admixed populations are scarce. We investigated the role of 10 polymorphisms in the microRNA and protein-coding genes of the microRNA synthesis complex in susceptibility to pediatric B-cell ALL. The study includes 100 pediatric ALL patients and 180 healthy individuals. The statistical analyses were run in SPSS v.25.0. In the case of the microRNA synthesizing genes, a significant pattern was found in only gene, that is, the rs3805500 polymorphism of DROSHA , in which the homozygous mutant (AA) genotype was associated with a threefold increase in the risk of developing ALL when compared to other genotypes (P=0.004, OR=2.913, CI=1.415-5.998). In the microRNA coding genes, the homozygous mutant rs3746444 genotype of the MIR499A gene was associated with a 17-fold increase in the risk of development of ALL (P<0.001, OR=17.797, CI=5.55-57.016). A protective effect against the development of ALL was also observed in the carriers of the wild homozygous rs2505901 genotype in the MIR938 gene. Our findings highlight the potential of these polymorphisms in the genes involving in the coding of microRNAs for the evaluation of the risk of contracting ALL in the population of the Brazilian Amazon region. These findings contribute to a more complete understanding of the complex etiology of ALL., Competing Interests: None., (AJTR Copyright © 2020.)

Aurora kinases (AURKA and AURKB) are mitotic kinases with an important role in the regulation of several mitotic events, and in hematological malignancies, AURKA and AURKB hyperexpression are found in patients with cytogenetic abnormalities presenting a unfavorable prognosis. The aim of this study was evaluated the mRNA expression profile of pediatric Acute Lymphoblastic Leukaemia (ALL) patients and the efficacy of two AURKA and AURKB designed inhibitors (GW809897X and GW806742X) in a leukemia cell line as a potential novel therapy for ALL patients. Cellular experiments demonstrated that both inhibitors induced cell death with caspase activation and cell cycle arrest, however only the GW806742X inhibitor decreased with more efficacy AURKA and AURKB expression in K-562 leukemia cells. In ALL patients both AURKA and AURKB showed a significant overexpression, when compared to health controls. Moreover, AURKB expression level was significant higher than AURKA in patients, and predicted a poorer prognosis with significantly lower survival rates. No differences were found in AURKA and AURKB expression between gene fusions, immunophenotypic groups, white blood cells count, gender or age. In summary, the results in this study indicates that the AURKA and AURKB overexpression are important findings in pediatric ALL, and designed inhibitor, GW806742X tested in vitro were able to effectively inhibit the gene expression of both aurora kinases and induce apoptosis in K-562 cells, however our data clearly shown that AURKB proves to be a singular finding and potential prognostic biomarker that may be used as a promising therapeutic target to those patients.

Copy number variations (CNVs) analysis may reveal molecular biomarkers and provide information on the pathogenesis of acute lymphoblastic leukemia (ALL). We investigated the gene copy number in childhood ALL by microarray and select three new recurrent CNVs to evaluate by real-time PCR assay: DMBT1 , KIAA0125 and PRDM16 were selected due to high frequency of CNVs in ALL samples and based on their potential biological functions in carcinogenesis described in the literature. DBMT1 deletion was associated with patients with chromosomal translocations and is a potential tumor suppressor; KIAA0125 and PRDM16 may act as an oncogene despite having a paradoxical behavior in carcinogenesis. This study reinforces that microarrays/aCGH is it is a powerful tool for detection of genomic aberrations, which may be used in the risk stratification., Competing Interests: Competing interestsThe authors declared that they have no conflict of interest., (© The Author(s) 2020.)

Acute Lymphoblastic Leukemia (ALL) is the most common cancer in children. Differences are found among ethnic groups in the results of the treatment of pediatric ALL. In general, children with a high level of native American ancestry tend to respond less positively to ALL treatments, which may be related to specific genomic variants found in native American groups. Despite the evidence, few data are available on the distribution of the pharmacogenomic variants relevant to the treatment of ALL in traditional Amerindian populations, such the those of the Amazon region. Given this, the present study investigated 27 molecular markers related to the treatment of ALL in Amerindians from Brazilian Amazonia and compared the frequencies with those recorded previously on five continents, that are available in the 1,000 Genomes database. The variation in the genotype frequencies among populations was evaluated using Fisher's exact test. The False Discovery Rate method was used to correct the results of the multiple analyses. Significant differences were found in the frequencies of the majority of markers between the Amerindian populations and those of other regions around the world. These findings highlight the unique genetic profile of the indigenous population of Brazilian Amazonia, which may reflect a distinct therapeutic profile for the treatment of ALL in these populations.

Introduction: The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil., Methods: The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software., Results: Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world., Conclusion: Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines., Competing Interests: The authors have declared that no competing interests exist.

Acute Lymphoblastic Leukemia (ALL) is the most common childhood neoplasia. Studies have shown that susceptibility to ALL may be modulated by genetic variables. Our study investigated 21 genetic variants in the susceptibility of the population of the Brazilian Amazon region to B-cell ALL. The variants of the genes GGH, CEBPE, ARID5B, MTHFR and MTHFD1 were related to a protective effect against the development of ALL, whereas the variant of the gene ATIC was associated with a risk effect. The results suggest that genetic variants analyzed modulate of the risk of developing ALL in the studied population., Competing Interests: The authors declare that they have no competing interests., (© 2019 The Authors.)

The treatment of Acute Lymphoblastic Leukemia (ALL) in children has a high clinical success rate, although toxicological complications are frequent, and often result in the interruption of the treatment. Various studies have shown that toxicities resulting from the treatment are influenced by pharmacogenetic variants. Most of this research has focused on relatively homogeneous populations, and the influence of these variants in highly admixed populations, such as that of Brazil, is still poorly understood. The present study investigated the association between pharmacogenetic variants and severe toxicities in pediatric B-cell ALL patients from an admixed population of the Brazilian Amazon. The rs2306283 (of SLCO1B1) mutant allele increased the risk of neurotoxicity threefold, and the homozygous mutant rs9895420 (of ABCC3) genotype was associated with a fivefold increase in protection against severe gastrointestinal toxicity. This indicates that the rs2306283 and rs9895420 polymorphisms may be relevant to the prediction of severe toxicity in pediatric ALL patients., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Acute lymphoblastic leukemia (ALL) is a malignant tumor common in children. Studies of genetic susceptibility to cancer using biallelic insertion/deletion (INDEL) type polymorphisms associated with cancer development pathways may help to clarify etymology of ALL. In this study, we investigate the role of eight functional INDEL polymorphisms and influence of genetic ancestry to B-cell ALL susceptibility in children of Brazilian Amazon population, which has a high degree of inter-ethnic admixture. Ancestry analysis was estimated using a panel of 48 autosomal ancestry informative markers. 130 B-cell ALL patients and 125 healthy controls were included in this study. The odds ratios and 95% confidence intervals were adjusted for confounders. The results indicated an association between the investigated INDEL polymorphisms in CASP8 (rs3834129), CYP19A1 (rs11575899) e XRCC1 (rs3213239) genes in the development of B-cell ALL. The carriers of Insertion/Insertion (Ins/Ins) genotype of the polymorphism in CASP8 gene presented reduced chances of developing B-cell ALL (P=0.001; OR=0.353; 95% CI=0.192-0.651). The Deletion/Deletion (Del/Del) genotype of the polymorphism in CYP19A1 gene was associated to a lower chance of developing B-cell ALL (P=3.35×10 -6 ; OR=0.121; 95% CI=0.050-0.295), while Del/Del genotype of the polymorphism in XRCC1 gene was associated to a higher chance of developing B-cell ALL (P=2.01×10 -4 ; OR=6.559; 95% CI=2.433-17.681). We also found that Amerindian ancestry correlates with the risk of B-cell ALL. For each increase of 10% in the Amerindian ancestry results in 1.4-fold chances of developing B-cell ALL (OR=1.406; 95% IC=1.123-1.761), while each increase of 10% in the European ancestry presents a protection effect in the development of B-cell ALL (OR=0.666; 95% IC=0.536-0.827). The results suggest that genetic factors influence leukemogenesis and might be explored in the stratification of B-cell ALL risk in admixed populations., (Copyright © 2015 Z. Published by Elsevier Ltd.. All rights reserved.)