Search

Background: Recurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1 plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5 , CDKN2A/2B , or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1 plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B , and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL., Methods: A total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation., Results: We identified the IKZF1 plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age ( p=0.04 ), a trend toward high-risk stratification ( p=0.06 ), and a decrease in 5-year Overall Survival (OS) ( p=0.009 ) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1 MUT group was older at diagnosis ( p=0.0002 ), and most of them were classified as high-risk (73.8%, p=0.02 ), while patients with CDKN2A/2B MUT had a higher leukocyte count ( p=0.01 ) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05 ) than the non-mutated patients. A decrease in OS was found in IKZF1 MUT and CDKN2A/2B MUT patients, but the significance was lost after IKZF1 plus was removed., Discussion: Our findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer, AM, declared a shared affiliation with the author RE-E to the handling editor at the time of review., (Copyright © 2024 Garcia-Solorio, Núñez-Enriquez, Jiménez-Olivares, Flores-Lujano, Flores-Espino, Molina-Garay, Cervera, Casique-Aguirre, Peñaloza-Gonzalez, Baños-Lara, García-Soto, Galván-Díaz, Olaya-Vargas, Aguilar, Mata-Rocha, Garrido-Hernández, Solís-Poblano, Luna-Silva, Cano-Cuapio, Aristil-Chery, Herrera-Quezada, Carrillo-Sanchez, Muñoz-Rivas, Flores-Lagunes, Mendoza-Caamal, Villegas-Torres, González-Osnaya, Jiménez-Hernández, Torres-Nava, Martín-Trejo, Gutiérrez-Rivera, Espinosa-Elizondo, Merino-Pasaye, Pérez-Saldívar, Jiménez-Morales, Curiel-Quesada, Rosas-Vargas, Mejía-Arangure and Alaez-Verson.)

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC)., Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained., Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed., Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer IO declared a shared affiliation with the author RE-E to the handling editor at the time of review., (Copyright © 2024 Duarte-Rodríguez, Flores-Lujano, McNally, Pérez-Saldivar, Jiménez-Hernández, Martín-Trejo, Espinoza-Hernández, Medina-Sanson, Paredes-Aguilera, Merino-Pasaye, Velázquez-Aviña, Torres-Nava, Espinosa-Elizondo, Amador-Sánchez, Dosta-Herrera, Mondragón-García, González-Ulibarri, Martínez-Silva, Espinoza-Anrubio, Paz-Bribiesca, Salcedo-Lozada, Landa-García, Ramírez-Colorado, Hernández-Mora, Santamaría-Ascencio, López-Loyola, Godoy-Esquivel, García-López, Anguiano-Ávalos, Mora-Rico, Castañeda-Echevarría, Rodríguez-Jiménez, Cibrian-Cruz, Solís-Labastida, Cárdenas-Cardos, López-Santiago, Flores-Villegas, Peñaloza-González, González-Ávila, Sánchez-Ruiz, Rivera-Luna, Rodríguez-Villalobos, Hernández-Pérez, Olvera-Durán, García-Cortés, Mata-Rocha, Sepúlveda-Robles, Bekker-Méndez, Jiménez-Morales, Meléndez-Zajgla, Rosas-Vargas, Vega, Núñez-Enríquez and Mejía-Aranguré.)

Background: Childhood cancer is the leading cause of disease-related mortality among children aged 5-14 years in Mexico, with acute leukemia being the most common cancer among infants. Examining the overall dietary patterns allows for a comprehensive assessment of food and nutrient consumption, providing a more predictive measure of disease risk than individual foods or nutrients. This study aims to evaluate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in Mexican infants., Methods: A hospital-based case-control study was conducted, comparing 109 confirmed acute leukemia cases with 152 age-matched controls. All participants (≤24 months) were identified at hospitals in Mexico City between 2010 and 2019. Data on a posteriori dietary patterns and other relevant variables were collected through structured interviews and dietary questionnaires. Multivariate logistic regression was employed to estimate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in infants., Results: The "Balanced & Vegetable-Rich" pattern, characterized by a balanced consumption of various food groups and higher vegetable intake, exhibited a negative association with acute leukemia when compared to the "High Dairy & Cereals" Pattern (adjusted odds ratio [OR] = 0.51; 95% confidence interval [CI]: 0.29, 0.90). We observed that mothers who gave birth to girls and adhered to a healthy dietary pattern during pregnancy exhibited significantly lower odds of their children developing AL compared to those who gave birth to boys [OR = 0.32 (95% CI 0.11, 0.97)]. Our results underscore the significance of maternal nutrition as a modifiable factor in disease prevention and the importance of prenatal health education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Muñoz-Aguirre, Denova-Gutiérrez, Pérez-Saldivar, Espinoza-Hernández, Dorantes-Acosta, Torres-Nava, Solís-Labastida, Paredes-Aguilera, Velázquez-Aviña, Espinosa-Elizondo, Miranda-Madrazo, González-Ávila, Rodríguez-Villalobos, Dosta-Herrera, Mondragón-García, Castañeda-Echevarría, López-Caballero, Martínez-Silva, Rivera-González, Hernández-Pineda, Flores-Botello, Pérez-Gómez, Rodríguez-Vázquez, Torres-Valle, Olvera-Durán, Martínez-Ríos, García-Cortés, Almeida-Hernández, Flores-Lujano, Núñez-Enriquez, Mata-Rocha, Rosas-Vargas, Duarte-Rodríguez, Jiménez-Morales, Mejía-Aranguré and López-Carrillo.)

Introduction: Maternal dietary consumption during pregnancy has been inconclusively associated with acute leukemia (AL) in infants, probably because epidemiological evidence has emerged mainly from the analysis of one-by-one nutrient, which is not a real-life scenario. Our objective was to evaluate the association between AL in Mexican children under 2 years of age and their mothers' nutrients concomitant intake during pregnancy, as well as to explore whether there are differences between girls and boys., Methods: We conducted a study of 110 cases of AL and 252 hospital-based controls in the Mexico City Metropolitan area from 2010 to 2019. We obtained information on maternal intake of 32 nutrients by a food frequency questionnaire and used weighted quantile sum regression to identify nutrient concomitant intakes., Results: We found a concomitant intake of nutrients negatively associated with AL (OR 0.17; CI95% 0.03,0.88) only among girls; and we did not find a nutrient concomitant intake positively associated with AL., Discussion: This is the first study that suggests nutrients that have been individually associated with AL are not necessarily the same in the presence of other nutrients (concomitant intake); as well as that maternal diet might reduce AL risk only in girls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mérida-Ortega, Pérez-Saldivar, Espinoza-Hernández, Dorantes-Acosta, Torres-Nava, Solís-Labastida, Paredes-Aguilera, Velázquez-Aviña, Espinosa-Elizondo, Miranda-Madrazo, González-Ávila, Rodríguez-Villalobos, Dosta-Herrera, Mondragón-García, Castañeda-Echevarría, López-Caballero, Martínez-Silva, Rivera-González, Hernández-Pineda, Flores-Botello, Pérez-Gómez, Rodríguez-Vázquez, Torres-Valle, Olvera-Durán, Martínez-Ríos, García‐Cortés, Almeida-Hernández, Flores-Lujano, Núñez-Enríquez, Mata-Rocha, Rosas-Vargas, Duarte-Rodríguez, Jiménez-Morales, Mejía-Arangure and López-Carrillo.)

Background: The distribution of RUNX1-RUNXT1 , PML-RARA , CBFB-MYH11 , BCR-ABL1 p210 , and KMT2A-MLLT3 in the pediatric population with acute myeloid leukemia (AML) in many countries of Latin America is largely unknown. Therefore, we aimed to investigate the frequency of these fusion genes in children with de novo AML from Mexico City, which has one of the highest incidence rates of acute leukemia in the world. Additionally, we explored their impact in mortality during the first year of treatment., Methods: We retrospectively analyzed the presence of RUNX1-RUNXT1 , PML-RARA , CBFB-MYH11 , BCR-ABL1 p210 , and KMT2A-MLLT3 by RT-PCR among 77 patients (<18 years) diagnosed with de novo AML between 2019 and 2021 in nine Mexico City hospitals., Results: The overall frequency of the fusion genes was 50.7%; RUNX1-RUNXT1 (22.1%) and PML-RARA (20.8%) were the most prevalent, followed by CBFB-MYH11 (5.2%) and BCR-ABL1 p210 (2.4%). KMT2A-MLLT3 was not detected. Patients with PML-RARA showed the lowest survival with high early mortality events. However, more studies are required to evaluate the impact of analyzed fusion genes on the overall survival of the Mexican child population with AML., Conclusion: The pediatric population of Mexico City with AML had frequencies of AML1-ETO , PML-RARA , CBFB-MYH11 , and BCR-ABL1 p210 similar to those of other populations around the world. Patients with BCR-ABL1 p210 and CBFB-MYH11 were few or did not die, while those with MLL-AF9 was not detected. Although patients with PML-RARA had a low survival and a high early mortality rate, further studies are needed to determine the long-term impacts of these fusion genes on this Latino population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Sepúlveda-Robles, Jiménez-Hernández, Domínguez-Catzín, Gómez-Flores, Martín-Trejo, Flores-Lujano, Torres-Nava, Núñez-Enríquez, De Ita, Medina Sanson, Mata-Rocha, Morales-Castillo, Bravata-Alcántara, Nájera-Cortés, Sánchez-Escobar, Peñaloza-Gonzalez, Espinosa-Elizondo, Flores-Villegas, Amador-Sánchez, Orozco-Ruiz, Pérez-Saldívar, Velázquez-Aviña, Merino-Pasaye, Solís-Labastida, González-Ávila, Santillán-Juárez, Bekker-Méndez, Jiménez-Morales, Rangel-López, Rosas-Vargas and Mejía-Aranguré.)

NK cells have unique attributes to react towards cells undergoing malignant transformation or viral infection. This reactivity is regulated by activating or inhibitory germline encoded receptors. An impaired NK cell function may result from an aberrant expression of such receptors, a condition often seen in patients with hematological cancers. Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer worldwide and NK cells have emerged as crucial targets for developing immunotherapies. However, there are important gaps concerning the phenotype and behavior of NK cells during emergence of ALL. In this study we analyze the phenotype and function of NK cells from peripheral blood in pediatric patients with ALL at diagnosis. Our results showed that NK cells exhibited an altered phenotype highlighted by a significant reduction in the overall expression and percent representation of activating receptors compared to age-matched controls. No significant differences were found for the expression of inhibitory receptors. Moreover, NK cells with a concurrent reduced expression in various activating receptors, was the dominant phenotype among patients. An alteration in the relative frequencies of NK cells expressing NKG2A and CD57 within the mature NK cell pool was also observed. In addition, NK cells from patients displayed a significant reduction in the ability to sustain antibody-dependent cellular cytotoxicity (ADCC). Finally, an aberrant expression of activating receptors is associated with the phenomenon of leukemia during childhood., Competing Interests: Authors JDW, KWH, and KPM are employed by GlaxoSmithKline. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Valenzuela-Vázquez, Nuñez-Enriquez, Sánchez-Herrera, Medina-Sanson, Pérez-Saldivar, Jiménez-Hernández, Martiín-Trejo, Del Campo-Martínez, Flores-Lujano, Amador-Sánchez, Mora-Ríos, Peñaloza-González, Duarte-Rodríguez, Torres-Nava, Espinosa-Elizondo, Cortés-Herrera, Flores-Villegas, Merino-Pasaye, Almeida-Hernández, Ramírez-Colorado, Solís-Labastida, Medrano-López, Pérez-Gómez, Velázquez-Aviña, Martínez-Ríos, Aguilar-De los Santos, Santillán-Juárez, Gurrola-Silva, García-Velázquez, Mata-Rocha, Hernández-Echáurregui, Sepúlveda-Robles, Rosas-Vargas, Mancilla-Herrera, Jimenez-Morales, Hidalgo-Miranda, Martinez-Duncker, Waight, Hance, Madauss, Mejía-Aranguré and Cruz-Munoz.)

Introduction: Over the years, the Hispanic population living in the United States has consistently shown high incidence rates of childhood acute leukemias (AL). Similarly, high AL incidence was previously observed in Mexico City (MC). Here, we estimated the AL incidence rates among children under 15 years of age in MC during the period 2010-2017., Methods: The Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia conducted a study gathering clinical and epidemiological information regarding children newly diagnosed with AL at public health institutions of MC. Crude age incidence rates (cAIR) were obtained. Age-standardized incidence rates worldwide (ASIRw) and by municipalities (ASIRm) were calculated by the direct and indirect methods, respectively. These were reported per million population <15 years of age; stratified by age group, sex, AL subtypes, immunophenotype and gene rearrangements., Results: A total of 903 AL cases were registered. The ASIRw was 63.3 (cases per million) for AL, 53.1 for acute lymphoblastic leukemia (ALL), and 9.4 for acute myeloblastic leukemia. The highest cAIR for AL was observed in the age group between 1 and 4 years (male: 102.34 and female: 82.73). By immunophenotype, the ASIRw was 47.3 for B-cell and 3.7 for T-cell. The incidence did not show any significant trends during the study period. The ASIRm for ALL were 68.6, 66.6 and 62.8 at Iztacalco, Venustiano Carranza and Benito Juárez, respectively, whereas, other municipalities exhibited null values mainly for AML., Conclusion: The ASIRw for childhood AL in MC is among the highest reported worldwide. We observed spatial heterogeneity of rates by municipalities. The elevated AL incidence observed in Mexican children may be explained by a combination of genetic background and exposure to environmental risk factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Flores-Lujano, Duarte-Rodríguez, Jiménez-Hernández, Martín-Trejo, Allende-López, Peñaloza-González, Pérez-Saldivar, Medina-Sanson, Torres-Nava, Solís-Labastida, Flores-Villegas, Espinosa-Elizondo, Amador-Sánchez, Velázquez-Aviña, Merino-Pasaye, Núñez-Villegas, González-Ávila, del Campo-Martínez, Alvarado-Ibarra, Bekker-Méndez, Cárdenas-Cardos, Jiménez-Morales, Rivera-Luna, Rosas-Vargas, López-Santiago, Rangel-López, Hidalgo-Miranda, Vega, Mata-Rocha, Sepúlveda-Robles, Arellano-Galindo, Núñez-Enríquez and Mejía-Aranguré.)

Background: In Mexico, the incidence of acute myeloid leukemia (AML) has increased in the last few years. Mortality is higher than in developed countries, even though the same chemotherapy protocols are used. CCAAT Enhancer Binding Protein Alpha ( CEBPA ) mutations are recurrent in AML, influence prognosis, and help to define treatment strategies. CEBPA mutational profiles and their clinical implications have not been evaluated in Mexican pediatric AML patients., Aim of the Study: To identify the mutational landscape of the CEBPA gene in pediatric patients with de novo AML and assess its influence on clinical features and overall survival (OS)., Materials and Methods: DNA was extracted from bone marrow aspirates at diagnosis. Targeted massive parallel sequencing of CEBPA was performed in 80 patients., Results: CEBPA was mutated in 12.5% (10/80) of patients. Frameshifts at the N-terminal region were the most common mutations 57.14% (8/14). CEBPA biallelic ( CEBPA BI ) mutations were identified in five patients. M2 subtype was the most common in CEBPA positive patients ( CEBPA POS ) ( p = 0.009); 50% of the CEBPA POS patients had a WBC count > 100,000 at diagnosis ( p = 0.004). OS > 1 year was significantly better in CEBPA negative ( CEBPA NEG ) patients ( p = 0.0001). CEBPA POS patients (either bi- or monoallelic) had a significantly lower OS ( p = 0.002). Concurrent mutations in FLT3 , CSF3R , and WT1 genes were found in CEBPA POS individuals. Their contribution to poor OS cannot be ruled out., Conclusion: CEBPA mutational profiles in Mexican pediatric AML patients and their clinical implications were evaluated for the first time. The frequency of CEBPA POS was in the range reported for pediatric AML (4.5-15%). CEBPA mutations showed a negative impact on OS as opposed to the results of other studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Molina Garay, Carrillo Sánchez, Flores Lagunes, Jiménez Olivares, Muñoz Rivas, Villegas Torres, Flores Aguilar, Núñez Enríquez, Jiménez Hernández, Bekker Méndez, Torres Nava, Flores Lujano, Martín Trejo, Mata Rocha, Medina Sansón, Espinoza Hernández, Peñaloza Gonzalez, Espinosa Elizondo, Flores Villegas, Amador Sanchez, Pérez Saldívar, Sepúlveda Robles, Rosas Vargas, Jiménez Morales, Galindo Delgado, Mejía Aranguré and Alaez Verson.)

Background: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most frequent pediatric cancer worldwide. Despite improvements in treatment regimens, approximately 20% of the cases cannot be cured, highlighting the necessity for identifying new biomarkers to improve the current clinical and molecular risk stratification schemes. We aimed to investigate whether LINC00173 is a biomarker in ALL and to explore its expression level in other human cancer types., Methods: A nested case-control study including Mexican children with BCP-ALL was conducted. LINC00173 expression was evaluated by qRT-PCR using hydrolysis probes. To validate our findings, RNA-seq expression data from BCP-ALL and normal tissues were retrieved from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Genotype-Tissue Expression (GTEx) repositories, respectively. LINC00173 expression was also evaluated in solid tumors by downloading available data from The Cancer Genome Atlas (TCGA)., Results: A lower expression of LINC00173 in BCP-ALL cases compared to normal subjects was observed ( p < 0.05). ALL patients who carry the TCF3/PBX1 fusion gene displayed lower expression of LINC00173 in contrast to other BCP-ALL molecular subtypes ( p < 0.04). LINC00173 underexpression was associated with a high risk to relapse (HR = 1.946, 95% CI = 1.213-3.120) and die (HR = 2.073, 95% CI = 1.211-3.547). Patients with TCF3/PBX1 and underexpression of LINC00173 had the worst prognosis (DFS: HR = 12.24, 95% CI = 5.04-29.71; OS: HR = 11.19, 95% CI = 26-32). TCGA data analysis revealed that underexpression of LINC00173 is also associated with poor clinical outcomes in six new reported tumor types., Conclusion: Our findings suggest that LINC00173 is a biomarker of poor prognosis in BCP-ALL and other types of cancer. We observed an association between the expression of LINC00173 and TCF3/PBX1 and the risk to relapse and die in BCP-ALL, which is worse in TCF3/PBX1- positive cases displaying underexpression of LINC00173. Experimental studies are needed to provide insight into the LINC00173 and TCF3/PBX relationship., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 May-Hau, Bárcenas-López, Núñez-Enríquez, Bekker-Méndez, Beltrán-Anaya, Jiménez-Hernández, Ortíz-Maganda, Guerra-Castillo, Medina-Sanson, Flores-Lujano, Martín-Trejo, Peñaloza-González, Velázquez-Aviña, Torres-Nava, Hernández-Echáurregui, Espinosa-Elizondo, Gutiérrez-Rivera, Sanchez-Hernandez, Pérez-Saldívar, Flores-Villegas, Merino-Pasaye, Duarte-Rodríguez, Mata-Rocha, Sepúlveda-Robles, Rosas-Vargas, Hidalgo-Miranda, Mejía-Aranguré and Jiménez-Morales.)

ETV6::RUNX1 is a genetic rearrangement of good prognosis in children with acute lymphoblastic leukemia (ALL). In Mexico, its prevalence is low in comparison with Caucasian populations. We developed a novel TaqMan one-step RT-qPCR approach to assess the prevalence of four genetic rearrangements in a cohort of Hispanic children with ALL from Mexico City. The prevalence of common fusion gene transcripts was as follows: TCF3::PBX1 7.7%; BCR::ABL1p 190 3.3%; and KMT2A::AFF1 2.8%, and ETV6::RUNX1 was observed with low prevalence (10.5%) in comparison to that reported for developed countries. This is consistent with previous findings on Mexican children with ALL and similar to those reported on children from Hispanic populations. The confirmation of a low prevalence of ETV6::RUNX1 in children of a Hispanic origin represents an advancement in the description of genetic factors of ALL in these populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mata-Rocha, Rangel-López, Jimenez-Hernandez, Nuñez-Enríquez, Morales-Castillo, Sánchez-Escobar, Sepúlveda-Robles, Bravata-Alcántara, Nájera-Cortés, Pérez-Saldivar, Flores-Lujano, Duarte-Rodríguez, Oviedo de Anda, Romero Tlalolini, Alaez Verson, Martín-Trejo, Muñoz Medina, Gonzalez-Bonilla, Hernandez Cueto, Bekker-Méndez, Jiménez-Morales, Medina-Sansón, Amador-Sánchez, Peñaloza-González, Torres-Nava, Espinosa-Elizondo, Cortés-Herrera, Flores-Villegas, Merino-Pasaye, Gutierrez-Rivera, Velazquez-Aviña, Santillan-Juarez, Gurrola-Silva, Hernández Echáurregui, Hidalgo-Miranda, Arellano Galindo, Rosas-Vargas and Mejía-Aranguré.)

Background: Acute lymphoblastic leukemia (ALL) is characterized by an abnormal proliferation of immature lymphocytes, in whose development involves both environmental and genetic factors. It is well known that single nucleotide polymorphisms (SNPs) in coding and noncoding genes contribute to the susceptibility to ALL. This study aims to determine whether SNPs in miR-146a , miR-196a-2 , miR-499a , and miR-612 genes are associated with the risk to ALL in pediatric Mexican population., Methods: A multicenter case-control study was carried out including patients with de novo diagnosis of ALL and healthy subjects as control group. The DNA samples were obtained from saliva and peripheral blood, and the genotyping of rs2910164, rs12803915, rs11614913, and rs3746444 was performed using the 5'exonuclease technique. Gene-gene interaction was evaluated by the multifactor dimensionality reduction (MDR) software., Results: miR-499a rs3746444 showed significant differences among cases and controls. The rs3746444G allele was found as a risk factor to ALL (OR, 1.6 [95% CI, 1.05-2.5]; p = 0.028). The homozygous GG genotype of rs3746444 confers higher risk to ALL than the AA genotype (OR, 5.3 [95% CI, 1.23-23.4]; p = 0.01). Moreover, GG genotype highly increases the risk to ALL in male group (OR, 17.6 [95% CI, 1.04-298.9]; p = 0.00393). In addition, an association in a gender-dependent manner among SNPs located in miR-146a and miR-196a-2 genes and ALL susceptibility was found., Conclusion: Our findings suggest that SNP located in miR-499a , miR-146a , and miR-196a-2 genes confer risk to ALL in Mexican children. Experimental analysis to decipher the role of these SNPs in human hematopoiesis could improve our understanding of the molecular mechanism underlying the development of ALL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jiménez-Morales, Núñez-Enríquez, Cruz-Islas, Bekker-Méndez, Jiménez-Hernández, Medina-Sanson, Olarte-Carrillo, Martínez-Tovar, Flores-Lujano, Ramírez-Bello, Pérez-Saldívar, Martín-Trejo, Pérez-Lorenzana, Amador-Sánchez, Mora-Ríos, Peñaloza-González, Duarte-Rodríguez, Torres-Nava, Flores-Bautista, Espinosa-Elizondo, Román-Zepeda, Flores-Villegas, Tamez-Gómez, López-García, Lara-Ramos, González-Ulivarri, Martínez-Silva, Espinoza-Anrubio, Almeida-Hernández, Ramírez-Colorado, Hernández-Mora, García-López, Cruz-Ojeda, Godoy-Esquivel, Contreras-Hernández, Medina-Hernández, López-Caballero, Hernández-Pineda, Granados-Kraulles, Rodríguez-Vázquez, Torres-Valle, Cortés-Reyes, Medrano-López, Pérez-Gómez, Martínez-Ríos, Aguilar-De-los-Santos, Serafin-Díaz, Gutiérrez-Rivera, Merino-Pasaye, Vargas-Alarcón, Mata-Rocha, Sepúlveda-Robles, Rosas-Vargas, Hidalgo-Miranda and Mejía-Aranguré.)

Background: Refining risk stratification to avoid very early relapses (VER) in Mexican patients with B-lineage acute lymphoblastic leukemia (B-ALL) could lead to better survival rates in our population., Aim of the Study: The purpose of this study was to investigate the association between the United Kingdom ALL (UKALL)-CNA classifier and VER risk in Mexican patients with childhood B-ALL., Methods: A nested case-control study of 25 cases with VER and 38 frequency-matched controls without relapse was conducted within the MIGICCL study cohort. They were grouped into the categories of the UKALL-CNA risk classifier (good [reference], intermediate and poor), according to the results obtained by multiplex ligation dependent probe amplification. Overall and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards analyses were conducted., Results: The CDKN2A/B genes were most frequently deleted in the group with relapse. According to UKALL-CNA classifier, 33 (52.4%) patients were classified as good, 21 (33.3%) intermediate and 9 (14.3%) poor-risk B-ALL. The intermediate and poor risk groups were associated with an increased risk of VER (HR = 4.94, 95% CI = 1.87-13.07 and HR = 7.42, 95% CI = 2.37-23.26, respectively) in comparison to the good-risk patients. After adjusting by NCI risk classification and chemotherapy scheme in a multivariate model, the risks remained significant., Conclusions: Our data support the clinical utility of profiling CNAs to potentially refine current risk stratification strategies of patients with B-ALL., (Copyright © 2021 IMSS. Published by Elsevier Inc. All rights reserved.)

It is important to study the relationship between extremely low-frequency magnetic fields (ELF-MFs) and childhood leukemia, particularly in locations with a high incidence of this neoplasm in children and an elevated exposure to ELF-MF, such as Mexico City. The aim was to investigate the association between ELF-MF exposure and the risk of B-lineage acute lymphoblastic leukemia (B-ALL). A case-control study was conducted in Mexico City during the period from 2010 to 2011. Residential 24-h ELF-MF measurements were obtained for 290 incident B-ALL patients and 407 controls, aged less than 16 years. Controls were frequency-matched by sex, age (±18 months), and health institution. The adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated. ELF-MF exposure at <0.2 μT was used to define the reference group. ELF-MF exposure at ≥0.3 μT was observed in 11.3% of the controls. Different ELF-MF intensity cutoff values were used to define the highest exposure category; the highest exposure category for each cutoff value was associated with an increased risk of B-ALL compared with the corresponding lower exposure categories. The aORs were as follows: ≥0.2 μT = 1.26 (95% CI: 0.84-1.89); ≥0.3 μT = 1.53 (95% CI: 0.95-2.48); ≥0.4 μT = 1.87 (95% CI: 1.04-3.35); ≥0.5 μT = 1.80 (95% CI 0.95-3.44); ≥0.6 μT = 2.32 (95% CI: 1.10-4.93). ELF-MF exposure as a continuous variable (per 0.2 μT intervals) was associated with B-ALL risk (aOR = 1.06; 95% CI: 1.01-1.12). In the present study, the proportion of children exposed to ≥0.3 μT is among the highest reported worldwide. Additionally, an ELF-MF exposure ≥0.4 μT may be associated with the risk of B-ALL. Bioelectromagnetics. © 2020 Bioelectromagnetics Society., (© 2020 Bioelectromagnetics Society.)

Background: Acute lymphoblastic leukemia (ALL) is the main type of cancer in children. In Mexico and other Hispanic populations, the incidence of this neoplasm is one of the highest reported worldwide. Functional polymorphisms of various enzymes involved in the metabolism of xenobiotics have been associated with an increased risk of developing ALL, and the risk is different by ethnicity. The aims of the present study were to identify whether NQO1, CYP2E1 , and NAT2 polymorphisms or some genotype-environmental interactions were associated with ALL risk in Mexican children. Methods: We conducted a case-control study including 478 pediatric patients diagnosed with ALL and 284 controls (children without leukemia). Ancestry composition of a subset of cases and controls was assessed using 32 ancestry informative markers. Genetic-environmental interactions for the exposure to hydrocarbons were assessed by logistic regression analysis. Results: The polymorphisms rs1801280 (OR 1.54, 95% CI 1.21-1.93), rs1799929 (OR 1.96, 95% CI 1.55-2.49), and rs1208 (OR 1.44, 95% CI 1.14-1.81) were found to increase the risk of ALL; being the risks higher under a recessive model (OR 2.20, 95% CI 1.30-1.71, OR 3.87, 95% CI 2.20-6.80, and OR 2.26, 95% CI 1.32-3.87, respectively). Gene-environment interaction analysis showed that NAT2 rs1799929 TT genotype confers high risk to ALL under exposure to fertilizers, insecticides, hydrocarbon derivatives, and parental tobacco smoking. No associations among NQO1, CYP2E1 , and ALL were observed. Conclusion: Our study provides evidence for the association between NAT2 polymorphisms/gene-environment interactions, and the risk of childhood ALL in Mexican children., (Copyright © 2020 Medina-Sanson, Núñez-Enríquez, Hurtado-Cordova, Pérez-Saldivar, Martínez-García, Jiménez-Hernández, Fernández-López, Martín-Trejo, Pérez-Lorenzana, Flores-Lujano, Amador-Sánchez, Mora-Ríos, Peñaloza-González, Duarte-Rodríguez, Torres-Nava, Flores-Bautista, Espinosa-Elizondo, Román-Zepeda, Flores-Villegas, González-Ulivarri, Martínez-Silva, Espinoza-Anrubio, Almeida-Hernández, Ramírez-Colorado, Hernández-Mora, García-López, Cruz-Ojeda, Godoy-Esquivel, Contreras-Hernández, Medina-Hernández, López-Caballero, Hernández-Pineda, Granados-Kraulles, Rodríguez-Vázquez, Torres-Valle, Cortés-Reyes, Medrano-López, Pérez-Gómez, Martínez-Ríos, Aguilar-De los Santos, Serafin-Díaz, Bekker-Méndez, Mata-Rocha, Morales-Castillo, Sepúlveda-Robles, Ramírez-Bello, Rosas-Vargas, Hidalgo-Miranda, Mejía-Aranguré and Jiménez-Morales.)

Background: Acute myeloid leukemia (AML) is the second most frequent leukemia in childhood. The FLT3 gene participates in hematopoietic stem cell proliferation. FLT3 mutations are recurrent in AML and influence prognosis. In Mexican pediatric AML patients, FLT3 mutational profile, and their clinical impact have not been evaluated. Aim of the study: This study aimed to identify the profile of FLT3 mutations in pediatric patients with de novo AML and to assess their possible influence on overall survival (OS) and other clinical features. Methods: Massive parallel target sequencing of FLT3 was performed in 80 patients. Results: FLT3 mutations [internal tandem duplication (ITD) or tyrosine kinase domain (TKD)] were identified in 24% of them. OS was significantly lower in FLT3 POS cases than in FLT3 NEG ( p = 0.03). The average OS for FLT3 POS was 1.2 vs. 2.2 years in FLT3 NEG . There were no significant differences in the children's sex, age, percentage of blasts in bone marrow aspirate, or white blood cell count in peripheral blood at diagnosis between both groups. No differences were identified stratifying by the mutational load (high > 0.4) or type of mutation. The negative effect of FLT3 mutations was also observed in patients with acute promyelocytic leukemia (APL). Conclusions: FLT3 mutational profile is described in Mexican pediatric AML patients for the first time. Mutated FLT3 negatively impacts the outcome of AML patients, even considering the APL group. The clinical benefit from treatment with tyrosine kinase inhibitors in the FLT3 POS pediatric patients needs to be assessed in clinical trials. FLT3 testing may contribute to better risk stratification in our pediatric AML patients., (Copyright © 2020 Molina Garay, Carrillo Sánchez, Flores Lagunes, Jiménez Olivares, Muñoz Rivas, Villegas Torres, Flores Aguilar, Núñez Enríquez, Jiménez Hernández, Bekker Méndez, Torres Nava, Flores Lujano, Martín Trejo, Mata Rocha, Medina Sansón, Espinoza Hernández, Peñaloza Gonzalez, Espinosa Elizondo, Flores Villegas, Amador Sanchez, Pérez Saldívar, Sepúlveda Robles, Rosas Vargas, Rangel López, Domínguez López, García Latorre, Reyes Maldonado, Galindo Delgado, Mejía Aranguré and Alaez Verson.)

Background: The parental age at conception has been reported to be a risk factor for childhood acute leukaemia (AL); however, the relationship is controversial. The aim of the present study was to investigate the association between parental age at conception and the risk of AL in Mexican children, a population with a high incidence of the disease and a high prevalence of pregnancies in adolescents and young adults., Methods: A multicentre case-control study was conducted. Incident AL cases younger than 17 years of age diagnosed between 2010 and 2015 were included. Controls were matched with cases according to age, sex, and health institution. Using logistic regression analysis, adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) were calculated for each maternal stratum after adjusting for paternal age at conception of index child. The maternal age between 25 and 29.99 years was selected as the reference category., Results: In most strata where maternal and paternal ages were assessed, no association was found with the risk of developing acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring. An increased risk for AML was observed when the mother was between 20 and 24.99 years of age and the father aged 25-29.99 years (aOR, 1.94; 95 % CI, 1.03-3.67). In addition, there was a positive association for ALL when the mother´s age was between 20 and 24.99 years and the father was <20 years of age, however, a very wide confidence interval was noted (aOR, 12.26; 95 % CI, 1.41-106.83)., Conclusion: In the present study, maternal and paternal ages assessed in different strata showed little association with risk of developing ALL and AML in children. Positive associations between risk of both types of childhood AL were observed with younger paternal and maternal ages., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Evidence showing the role of long non-coding RNAs (lncRNAs) in leukemogenesis have emerged in the last decade. It has been proposed that these genes can be used as diagnosis and/or prognosis biomarkers in childhood acute lymphoblastic leukemia (ALL). To know if lncRNAs are associated with early relapse and early mortality, a microarray-based gene expression analysis in children with B-lineage ALL (B-ALL) was conducted. Cox regression analyses were performed. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated. LINC00152 and LINC01013 were among the most differentially expressed genes in patients with early relapse and early mortality. For LINC00152 high expression, the risks of relapse and death were HR: 4.16 (95% CI: 1.46-11.86) and HR: 1.99 (95% CI: 0.66-6.02), respectively; for LINC01013 low expression, the risks of relapse and death were HR: 3.03 (95% CI: 1.14-8.05) and HR: 6.87 (95% CI: 1.50-31.48), respectively. These results were adjusted by NCI risk criteria and chemotherapy regimen. The lncRNA-mRNA co-expression analysis showed that LINC00152 potentially regulates genes involved in cell substrate adhesion and peptidyl-tyrosine autophosphorylation biological processes. The results of the present study point out that LINC00152 could be a potential biomarker of relapse in children with B-ALL., Competing Interests: The authors declare no conflicts of interest.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children around the globe. Mexico City has one of the highest incidence rates of childhood leukemia worldwide with 49.5 cases per million children under the age of 15 which is similar to that reported for Hispanic populations living in the United States. In addition, it has been noted a dismal prognosis in Mexican and Hispanic ALL pediatric population. Although ALL, like cancer in general, has its origins in endogenous, exogenous, and genetic factors, several studies have shown that the immune system also plays a deterministic role in cancer development. Among various elements of the immune system, T lymphocytes and NK cells seem to dominate the immune response against leukemia. The aim of the present study was to perform a phenotypic and functional characterization of NK cells in ALL Mexican children at the moment of diagnosis and before treatment initiation. A case-control study was conducted by the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL). 41 cases were incident ALL children younger than 17 years old and residents of Mexico City. 14 controls were children without leukemia, matched by age and sex with cases. NK cell function was evaluated by degranulation assays towards K562 cells and SLAM-associated protein (SAP) expression was measured by intracellular staining. All assays were performed using peripheral blood mononuclear cells from controls and patients. The results indicate that NK mediated cytotoxicity, measured by CD107a degranulation assays in response to K562 cells, was reduced in ALL patients compared to controls. Interestingly, an impaired NK cell killing of target cells was not equally distributed among ALL patients. In contrast to patients classified as high-risk, standard-risk patients did not display a significant reduction in NK cell-mediated cytotoxicity. Moreover, patients presenting a leukocyte count ≥ 50,000xmm3 displayed a reduction in NK-cell mediated cytotoxicity and a reduction in SAP expression, indicating a positive correlation between a reduced SAP expression and an impaired NK cell-mediated citotoxicity. In the present study it was observed that unlike patients with standard-risk, NK cells from children presenting high-risk ALL, harbor an impaired cytotoxicity towards K562 at diagnosis. In addition, NK cell function was observed to be compromised in patients with a leukocyte count ≥50,000xmm3, where also it was noticed a decreased expression of SAP compared to patients with a leukocyte count <50,000xmm3. These data indicate NK cell-mediated cytotoxicity is not equally affected in ALL patients, nevertheless a positive correlation between low SAP expression and decreased NK cell-mediated cytotoxicity was observed in ALL patients with a leukocyte count ≥50,000xmm3. Finally, an abnormal NK cell-mediated cytotoxicity may represent a prognostic factor for high-risk acute lymphoblastic leukemia., Competing Interests: The authors have declared that no competing interests exist.

Background: Mexico City has one of the highest incidences and mortality rates of acute lymphoblastic leukemia (ALL) in the world and a high frequency of early relapses (17%) and early mortality (15%). Otherwise, childhood overweight and obesity are reaching epidemic proportions. They have been associated with poor outcomes in children with ALL. The aim of present study was to identify if overweight and obesity are predictors of early mortality and relapse in Mexican children with ALL., Methods: A multicenter cohort study was conducted. ALL children younger than 15 years old were included and followed-up during the first 24 months after diagnosis. Overweight and obesity were classified according World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) criteria. Early mortality and early relapses were the main outcomes., Results: A total of 1070 children were analyzed. Overweight/obesity at diagnosis were predictors of early mortality (WHO: HR = 1.4, 95%CI:1.0-2.0; CDC: HR = 1.6, 95%CI:1.1-2.3). However, no associations between overweight (WHO: HR = 1.5, 95%CI:0.9-2.5; CDC: HR = 1.0; 95% CI:0.6-1.6) and obesity (WHO: HR = 1.5, 95%CI:0.7-3.2; CDC: HR = 1.4; 95%CI:0.9-2.3) with early relapse were observed., Conclusions: Overweight and obese patients embody a subgroup with high risk of dying during leukemia treatment.

Acute lymphoblastic leukemia is the most common type of childhood cancer worldwide. Mexico City has one of the highest incidences and mortality rates of this cancer. It has previously been recognized that chromosomal translocations are important in cancer etiology. Specific fusion genes have been considered as important treatment targets in childhood acute lymphoblastic leukemia (ALL). The present research aimed at the identification and characterization of novel fusion genes with potential clinical implications in Mexican children with acute lymphoblastic leukemia. The RNA-sequencing approach was used. Four fusion genes not previously reported were identified: CREBBP-SRGAP2B , DNAH14-IKZF1 , ETV6-SNUPN , ETV6-NUFIP1 . Although a fusion gene is not sufficient to cause leukemia, it could be involved in the pathogenesis of the disease. Notably, these new translocations were found in genes encoding for hematopoietic transcription factors which are known to play an important role in leukemogenesis and disease prognosis such as IKZF1 , CREBBP , and ETV6 . In addition, they may have an impact on the prognosis of Mexican pediatric patients with ALL, with the potential to be included in the current risk stratification schemes or used as therapeutic targets.

In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case-control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015. Controls were frequency-matched to the cases by age, sex, and health institution. Logistic regression analysis was performed adjusting risks by child's sex, overcrowding index, birth order, and mother's age at the time of pregnancy. Adjusted odds ratios (aORs) and 95% confidence intervals were calculated. A total of 1455 cases and 1455 controls were included. An evident association between ALL and child's birthweight ≥2500 g was found (aOR 2.06; 95% CI: 1.59, 2.66) and also, in those with birthweight ≥3500 g (aOR 1.19; 95% CI: 1.00, 1.41). In AML patients with birthweight ≥2500 g and ≥3500 g, an aOR of 1.77 (95% CI: 1.07, 2.94) and 1.42 (95% CI: 1.03-1.95) was observed, respectively. No association was noticed with either type of AL and a birthweight ≥4000 g. To sum up, we found a moderate association between not having a low birthweight and an increased risk of acute leukemias. Birthweight ≥3500 g was also a risk factor for both types of leukemia. This suggests that a greater birthweight may increase the risk of acute leukemias in Mexican children., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The role of malnutrition at diagnosis as a predictor of early mortality in Mexican leukemia children remains controversial. The objective of present study was to investigate whether malnutrition was a predictor of early mortality during the first year of treatment in Mexican acute lymphoblastic leukemia (ALL) children through the first population-based study. A total of 794 newly diagnosed ALL pediatric patients from public hospitals of Mexico City were enrolled. A multivariate Cox proportional hazards regression model was constructed and adjusted by patient's age at diagnosis, gender, hospital of treatment, and socioeconomic status. Early mortality was high (12.1%) and malnutrition by different indicators was not associated with mortality at induction phase and at 6th month; a high risk of dying (RR = 2.08; 95% CI: 1.08-4.01) was observed in the group of malnourished children with a high-risk ALL.

B-cell precursor acute lymphocytic leukemia (B-ALL) represents a worldwide public health issue. Particularly, Mexico is one of the countries with the highest incidence of ALL in children. Between the multiple factors involved in ALL etiology, genetic alterations are clearly one of the most relevant features. In this work, a group of 24 B-ALL patients, all negative for the four most frequent gene fusions (ETV6-RUNX1, BCR-ABL1, TCF3-PBX1 and MLL-AF4), were included in a high-resolution microarray analysis in order to evaluate genomic copy-number alterations (CNAs). The results of this preliminary report showed a broad genomic heterogeneity among the studied samples; 58% of the patients were hyperdiploid and 33% displayed a chromosome 9p deletion of variable length affecting genes CDKN2A/B, two patients displayed genomic instability with a high number of focal CNAs, three patients presented unique duplications affecting 2q, 12p and 1q, respectively, and one patient displayed no copy number imbalances. The copy-number profile of 44 genes previously related to B-ALL was heterogeneous as well. Overall results highlight the need for a detailed description of the genetic alterations in ALL cancer cells in order to understand the molecular pathogenesis of the disease and to identify any prognostic markers with clinical significance., (Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.)

Introduction: Acute myeloid leukemias represent the second most common childhood leukemia subtype. In Mexico, there are few studies on descriptive epidemiology for this disease., Aims: To report acute myeloid leukemia incidence for children less than 15 years of age in the Metropolitan Area of the Valley of Mexico for a period of five years (2010-2014) and to analyze whether there are differences in the incidence of acute myeloid leukemia by regions., Material and Methods: A descriptive study was conducted in nine public hospitals in Mexico City. The crude annual average incidence rate and adjusted average annual incidence rate were calculated., Results: A total of 190 patients with diagnosis of de novo acute myeloid leukemia were analyzed. Male sex (57.2%) and acute myeloid leukemia-M3 subtype (25.3%) were more frequent. The adjusted average annual incidence rates for Mexico City and for the Metropolitan Area of the Valley of Mexico were 8.18 and 7.74 per million children under 15 years old, respectively., Conclusions: It seems that childhood acute myeloid leukemia incidence is increasing in Mexico City, which makes the identification of associated risk factors imperative.

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis.

Background: In Mexico City, the incidence of childhood acute lymphoblastic leukemia (ALL) is one of the highest in the world; epidemiologic evidence suggests that infectious agents could be involved in the genesis of this disease. Early transmitted oncogenic retroviruses infecting lymphocytes are important candidates., Methods: PCR-based assays were used to screen viral genomic sequences of human T-cell lymphotrophic virus, type 1 (HTLV1) and mouse mammary tumor virus (MMTV)-like virus (MMTV-LV) in leukemic cells from 67 pediatric patients with ALL., Results: Viral genomic sequences were not detected in any sample by neither standard nor nested PCR., Conclusions: Because of the methodologic strictness and high statistical power of the study, these results suggest that HTLV1 and MMTV-LV are not involved in the genesis of childhood ALL in Mexican children., Impact: To our knowledge, this is the first work exploring the direct participation of HTLV1 and MMTV-LV retroviruses in childhood ALL development., (©2013 AACR.)