[Descriptive epidemiology of children with acute myeloid leukemia residing in Mexico City: a report from the Mexican Inter-Institutional Group for Identifying Childhood Leukemia Causes]. / Epidemiología descriptiva de la leucemia mieloide aguda (LMA) en niños residentes de la Ciudad de México: reporte del Grupo Mexicano Interinstitucional para la Identificación de las Causas de la Leucemia en Niños.

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.

Gene Expression Profiling of Acute Lymphoblastic Leukemia in Children with Very Early Relapse.

BACKGROUND AND AIMS: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer worldwide. Mexican patients have high mortality rates, low frequency of good prognosis biomarkers (i.e., ETV6-RUNX1) and a high proportion is classified at the time of diagnosis with a high risk to relapse according to clinical features. In addition, very early relapses are more frequently observed than in other populations. The aim of the study was to identify new potential biomarkers associated with very early relapse in Mexican ALL children through transcriptome analysis. METHODS: Microarray gene expression profiling on bone marrow samples of 54 pediatric ALL patients, collected at time of diagnosis and/or at relapse, was performed. Eleven patients presented relapse within the first 18 months after diagnosis. Affymetrix Human Transcriptome Array 2.0 (HTA 2.0) was used to perform gene expression analysis. Annotation and functional enrichment analyses were carried out using Gene Ontology, KEGG pathway analysis and Ingenuity Pathway Analysis tools. RESULTS: BLVRB, ZCCHC7, PAX5, EBF1, TMOD1 and BLNK were differentially expressed (fold-change >2.0 and p value <0.01) between relapsed and non-relapsed patients. Functional analysis of abnormally expressed genes revealed their important role in cellular processes related to the development of hematological diseases, cancer, cell death and survival and in cell-to-cell signaling interaction. CONCLUSIONS: Our data support previous findings showing the relevance of PAX5, EBF1 and ZCCHC7 as potential biomarkers to identify a subgroup of ALL children in high risk to relapse.

Copy Number Alterations Associated with Acute Lymphoblastic Leukemia in Mexican Children. A report from The Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.

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.