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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.)

Introduction: Acute leukemias (AL) are the main types of cancer in children worldwide. In Mexico, they represent one of the main causes of death in children under 20 years of age. Most of the studies on the incidence of AL in Mexico have been developed in the urban context of Greater Mexico City and no previous studies have been conducted in the central-south of the country through a population-based study. The aim of the present work was to identify the general and specific incidence rates of pediatric AL in three states of the south-central region of Mexico considered as some of the marginalized populations of Mexico (Puebla, Tlaxcala, and Oaxaca)., Methods: A population-based study was conducted. Children aged less than 20 years, resident in these states, and newly diagnosed with AL in public/private hospitals during the period 2021-2022 were identified. Crude incidence rates (cIR), standardized incidence rates (ASIRw), and incidence rates by state subregions (ASIRsr) were calculated. Rates were calculated using the direct and indirect method and reported per million children under 20 years of age. In addition, specific rates were calculated by age group, sex, leukemia subtype, and immunophenotype., Results: A total of 388 cases with AL were registered. In the three states, the ASIRw for AL was 51.5 cases per million (0-14 years); in Puebla, it was 53.2, Tlaxcala 54.7, and Oaxaca de 47.7. In the age group between 0-19 years, the ASIRw were 44.3, 46.4, 48.2, and 49.6, in Puebla, Tlaxcala, and Oaxaca, respectively. B-cell acute lymphoblastic leukemia was the most common subtype across the three states., Conclusion: The incidence of childhood AL in the central-south region of Mexico is within the range of rates reported in other populations of Latin American origin. Two incidence peaks were identified for lymphoblastic and myeloid leukemias. In addition, differences in the incidence of the disease were observed among state subregions which could be attributed to social factors linked to the ethnic origin of the inhabitants. Nonetheless, this hypothesis requires further investigation., 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 authors JN-E, RP and JM-A were all Topic Editors and were members of Frontiers at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Flores-Lujano, Allende-López, Duarte-Rodríguez, Alarcón-Ruiz, López-Carrillo, Shamah-Levy, Cebrián, Baños-Lara, Casique-Aguirre, Elizarrarás-Rivas, López-Aquino, Garrido-Hernández, Olvera-Caraza, Terán-Cerqueda, Martínez-José, Aristil-Chery, Alvarez-Rodríguez, Herrera-Olivares, Ruíz-Arguelles, Chavez-Aguilar, Márquez-Toledo, Cano-Cuapio, Luna-Silva, Martínez-Martell, Ramirez-Ramirez, Merino-Pasaye, Galván-Díaz, Medina-Sanson, Gutiérrez-Rivera, Martín-Trejo, Rodriguez-Cedeño, Bekker-Méndez, Romero-Tlalolini, Cruz-Maza, Juárez-Avendaño, Pérez-Tapia, Rodríguez-Espinosa, Suárez-Aguirre, Herrera-Quezada, Hernández-Díaz, Galván-González, Mata-Rocha, Olivares-Sosa, Rosas-Vargas, Jiménez-Morales, Cárdenas-González, Álvarez-Buylla Roces, Duque-Molina, Pelayo, Mejía-Aranguré and Núñez-Enriquez.)

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: Advances in the understanding of the pathobiology of childhood B-cell acute lymphoblastic leukemia (B-ALL) have led towards risk-oriented treatment regimens and markedly improved survival rates. However, treatment-related toxicities remain a major cause of mortality in developing countries. One of the most common adverse effects of chemotherapy in B-ALL is the hematologic toxicity, which may be related to genetic variants in membrane transporters that are critical for drug absorption, distribution, and elimination. In this study we detected genetic variants present in a selected group genes of the ABC and SLC families that are associated with the risk of high-grade hematologic adverse events due to chemotherapy treatment in a group of Mexican children with B-ALL., Methods: Next generation sequencing (NGS) was used to screen six genes of the ABC and seven genes of the SLC transporter families, in a cohort of 96 children with B-ALL. The grade of hematologic toxicity was classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, Subsequently, two groups of patients were formed: the null/low-grade (grades 1 and 2) and the high-grade (grades 3 to 5) adverse events groups. To determine whether there is an association between the genetic variants and high-grade hematologic adverse events, logistic regression analyses were performed using co-dominant, dominant, recessive, overdominant and log-additive inheritance models. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated., Results: We found two types of associations among the genetic variants identified as possible predictor factors of hematologic toxicity. One group of variants associated with high-grade toxicity risk: ABCC1 rs129081; ABCC4 rs227409; ABCC5 rs939338, rs1132776, rs3749442, rs4148575, rs4148579 and rs4148580; and another group of protective variants that includes ABCC1 rs212087 and rs212090; SLC22A6 rs4149170, rs4149171 and rs955434., Conclusion: There are genetic variants in the SLC and ABC transporter families present in Mexican children with B-ALL that can be considered as potential risk markers for hematologic toxicity secondary to chemotherapeutic treatment, as well as other protective variants that may be useful in addition to conventional risk stratification for therapeutic decision making in these highly vulnerable patients., 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 author JN-E was a review editor and JM-A was an associate editor, review editor and a guest associate editor. Both authors 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 © 2024 Escalante-Bautista, Cerecedo, Jiménez-Hernández, González-Torres, Gaytán-Cervantes, Núñez-Enríquez, Sepúlveda-Robles, De Ita, Jiménez-Morales, Sánchez-López, Mata-Rocha, Torres-Nava, Martín-Trejo, Flores-Villegas, Gutiérrez-Rivera, Merino-Pasaye, Solís-Labastida, Miranda-Madrazo, Hernández-Echáurregui, Orozco-Ruíz, Flores-Lujano, Pérez-Saldívar, Mejía-Aranguré and Rosas-Vargas.)

Introduction: Epidemiological studies around the world on acute leukemia (AL) and risk factors in infants are scarce. Infant AL has been proposed to originate in utero , which facilitates its study by establishing a short exposure time in pregnant women to environmental and dietary factors that could contribute to the risk of or protection against leukemia. We hypothesized that maternal diet during pregnancy may be an important factor involved in AL in offspring., Methods: We conducted a hospital-based case-control study from 2010 to 2019 on maternal diet during pregnancy in nine high-specialty public hospitals of different health institutions that diagnose and offer treatment to children with AL in Mexico City. Cases (n=109) were children ≤24 months of age with de novo diagnosis of AL, and controls (n=252) were children obtained in hospitals from second-level medical care matched for age, sex, and health institution. Maternal diet during pregnancy was obtained by a semiquantitative food frequency questionnaire. Unconditional logistic regression models were used to assess the association between food groups and infant AL. Potential confounders were assessed by constructing directed acyclic graphs (DAGs) with Dagitty software in which adjusted options were identified for the construction of unconditional logistic regression models., Results: Cases were slightly predominantly female (52.3%). The years of education of the mother in cases and controls was 0-9 on average, and those who reported smoking cigarettes and consuming alcohol during pregnancy did so at a low frequency. Regarding the mother's diet, the main findings were that the consumption of allium vegetables during pregnancy was inversely associated with AL for medium and high consumption (OR=0.26, 95% CI 0.14-0.46; P -trend< 0.001). In contrast, the high consumption of high-fat dairy products had a positive association with AL (OR=2.37, 95% CI 1.30-4.34; P -trend<0.001). No association was found between consumption of topoisomerase II inhibitor foods during pregnancy and AL., Conclusion: The results suggest that maternal intake during pregnancy of allium vegetables, specifically garlic, is inversely associated with the development of AL in children ≤24 months old. On the other hand, consumption of high-fat dairy products is positively associated with AL in children ≤24 months old., 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 © 2024 Pérez-Saldivar, Flores-García, Núñez-Villegas, Fajardo-Gutiérrez, Medina-Sanson, Jiménez-Hernández, Martín-Trejo, López-Santiago, Peñaloza-González, Cortés-Herrera, Merino-Pasaye, Amador-Sánchez, García-López, Pérez-Lorenzana, Román-Zepeda, Castañeda-Echevarría, López-Caballero, Martínez-Silva, Rivera-González, Granados-Kraulles, Flores-Botello, Medrano-López, Rodríguez-Vázquez, Torres-Valle, Mora-Rico, Mora-Ríos, R.García‐Cortés, Salcedo-Lozada, Flores-Lujano, Núñez-Enríquez, Bekker-Méndez, Mata-Rocha, Rosas-Vargas, Duarte-Rodríguez, Jiménez-Morales, Hidalgo-Miranda, López-Carrillo and Mejía-Aranguré.)

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.)

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.)

Mexico City has one of the highest incidences of acute lymphoblastic leukemia (ALL) globally, with patients showing low survival, and high relapse rates. To gain more insight into the molecular features of B-ALL in Mexican children, we isolated CD10 + /CD19 + precursor B lymphoblasts from four bone marrow and nine peripheral blood samples of B-ALL patients using a fluorescence-activated cell sorting protocol. The global gene expression profile (BM vs PB) revealed 136 differentially expressed genes; 62 were upregulated (45.6%) and 74 were downregulated (54.4%). Pearson's correlation coefficient was calculated to determine the similarity between pre-B lymphoblast populations. We selected 26 highly significant genes and validated 21 by RT-qPCR (CNN3, STON2, CALN1, RUNX2, GADD45A, CDC45, CDC20, PLK1, AIDA, HCK, LY86, GPR65, PIK3CG, LILRB2, IL7R, TCL1A, DOCK1, HIST1H3G, PTPN14, CD72, and NT5E). The gene set enrichment analysis of the total expression matrix and the ingenuity pathway analysis of the 136 differentially expressed genes showed that the cell cycle was altered in the bone marrow with four overexpressed genes (PLK1, CDC20, CDC45, and GADD45A) and a low expression of IL7R and PIK3CG, which are involved in B cell differentiation. A comparative bioinformatics analysis of 15 bone marrow and 10 peripheral blood samples from Hispanic B-ALL patients collected by the TARGET program, corroborated the genes observed, except for PIK3CG. We conclude the Mexican and the Hispanic B-ALL patients studied present common driver alterations and histotype-specific mutations that could facilitate risk stratification and diagnostic accuracy and serve as potential therapeutic targets., (© 2022. The Author(s).)

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.