[PCR detection of relevant translocations in pediatric acute lymphoblastic leukemia]. / Detección de translocaciones relevantes por PCR en pacientes pediátricos con leucemia linfoblástica aguda.

BACKGROUND: In Mexico, leukemia represents the most common type of cancer in the population under 15 years old with a high incidence rate when compared with developed countries. The etiology of leukemia may be unknown, however different factors are involve such as chromosomal translocations. The aim of this work is to detect the molecular alterations: TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1 in pediatric patients with acute lymphoblastic leukemia. METHODS: 91 bone marrow samples were collected from pediatric patients with acute lymphoblastic leukemia from january 2012 to march 2013 at the Pediatric Hematology Service, Hospital General "Gaudencio González Garza". Translocations detected (TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1) using real time PCR, SYBR Green (Qiagen, Alameda, CA). RESULTS: 91 samples were processed, the detected frequencies for each translocation were: TEL-AML1 (7.21%), E2A-PBX1 (5.15%). The MLL-AF4 and the BCR-ABL minor translocations were not detected in this study. CONCLUSIONS: The frequencies shown in this study are consistent with the data shown in the literature, where TEL-AML1 is the most common translocation found in pediatric patients. It is of relevance to mention that E2A-PBX1 is found in a high frequency in developing countries when compared with developed countries.

Introducción: en México, las leucemias representan el tipo de cáncer más frecuente en la población menor de 15 años con una tasa de incidencia alta cuando se compara con países desarrollados. La etiología de las leucemias puede ser desconocida, sin embargo se presentan distintos factores que pueden condicionar la enfermedad, tal es el caso de las translocaciones cromosómicas. El objetivo de este trabajo es detectar las alteraciones moleculares: TEL-AML1, MLL-AF4, BCR-ABL menor y E2A-PBX1 en los pacientes pediátricos con leucemia aguda linfoblástica. Métodos: se colectaron 91 muestras de médula ósea de enero de 2012 a marzo de 2013 de pacientes pediátricos con leucemia aguda linfoblástica del Servicio de Hematología. Se detectaron las translocaciones (TEL-AML1, MLL-AF4, BCR-ABL menor y E2A-PBX1) con técnicas moleculares de tiempo real con SYBR Green (Qiagen, Alameda, CA). Resultados: se procesaron 91 muestras, las frecuencias detectadas para cada una de las translocaciones fueron: TEL-AML1 (7.21%), E2A-PBX1 (5.15%). Las translocaciones MLL-AF4 y BCR-ABL menor no fueron detectadas en este estudio. Conclusiones: las frecuencias mostradas en este estudio están en concordancia con los datos mostrados en la literatura donde TEL-AML1 es la translocación más común encontrada en pacientes pediátricos. Es importante mencionar que E2A-PBX1 se encuentra en una frecuencia alta en países en vías de desarrollo al comparase con países desarrollados.

Analysis of Thiopurine S-Methyltransferase Deficient Alleles in Acute Lymphoblastic Leukemia Patients in Mexican Patients.

BACKGROUND AND AIMS: It has been demonstrated that heterozygote and homozygote thiopurine S-methyltransferase (TPMT) mutant allele carriers are at high risk to develop severe and potentially fatal hematopoietic toxicity after treatment with standard doses of 6-mercaptopurine (6-MP) and methotrexate (MX). Those drugs are the backbone of acute lymphoblastic leukemia (ALL) and several autoimmune disease treatments. We undertook this study to determine the frequency of the TPMT deficient alleles in children with ALL and non-ALL subjects from Mexico City and Yucatan, Mexico. METHODS: We included 849 unrelated subjects, of which 368 ALL children and 342 non-ALL subjects were from Mexico City, and 60 ALL cases and 79 non-ALL individuals were from Yucatan. Genotyping of the rs1800462, rs1800460 and rs1142345 SNPs was performed by 5'exonuclease technique using TaqMan probes (Life Technologies Foster City, CA). RESULTS: The mutant TPMT alleles were present in 4.8% (81/1698 chromosomes) and only 0.2% were homozygote TPMT*3A/TPMT*3A. We did not find statistically significant differences in the distribution of the mutant alleles between patients from Mexico City and Yucatan in either ALL cases or non-ALL. Nonetheless, the TPMT*3C frequency in ALL patients was higher than non-ALL subjects (p = 0.03). To note, the null homozygous TPMT*3A/TPMT*3A genotype was found in 2.5% of the non-ALL subjects. CONCLUSIONS: TPMT mutant alleles did not exhibit differential distribution between both evaluated populations; however, TPMT*3C is overrepresented in ALL cases in comparison with non-ALL group. Assessing the TPMT mutant alleles could benefit the ALL children and those undergoing 6-MP and MX treatment.

ARID5B, CEBPE and PIP4K2A Germline Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia in Mexican Patients: A MIGICCL Study.

BACKGROUND AND AIMS: Childhood acute lymphoblastic leukemia (ALL) is the leading cause of childhood cancer-related deaths worldwide. Multiples studies have shown that ALL seems to be originated by an interaction between environmental and genetic susceptibility factors. The ARID5B polymorphisms are among the most reproducible ALL associated-risk alleles in different populations. The aim of the present study was to examine the contribution of ARID5B, CEBPE, and PIP4K2 risk alleles for the development of ALL in children from Mexico City and Yucatan, Mexico. METHODS: A study was conducted with a total of 761 unrelated subjects. Two hundred eighty five ALL cases (111 from Yucatan and 174 from Mexico City) and 476 healthy subjects. Genotyping included the rs7088318 (PIP4K2A), rs10821936 (ARID5B), rs7089424 (ARID5B) and rs2239633 (CEBPE) polymorphisms. RESULTS: Associations between ALL and rs10821936 and rs7089424 ARID5B SNPs were found (OR = 1.9, 95% CI (1.5-2.4) and OR = 2.0, 95% CI (1.6-2.5), respectively). Moreover, a higher risk was observed in the homozygous risk genotypes of carriers from Mexico City (OR = 3.1, 95% CI (2.0-4.9) and OR 3.1, CI 95% (2.0-4.8), respectively). Otherwise, the rs7088318 (PIP4K2A) and rs2239633 (CEBPE) polymorphisms were not associated with ALL risk. CONCLUSIONS: Our analysis suggests that ARID5B confers risk for childhood ALL in a Mexican population.