Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

Abstract

Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child's diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.

Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

“…In our study, we lack any information regarding the status for MRD in our patients, however it will be interesting to evaluate in further studies a possible association between an abnormal NK cell-mediated cytotoxicity and MRD. In addition, in only 17.7% of ALL patients from Mexico City, the four most common gene rearrangements have been detected [14,46], making difficult to address how NK cell function may be affected by such genetic alterations in patients with ALL. With no doubt, this remain an interesting issue to be addressed in future studies.…”

Insights into the prenatal origin of childhood acute lymphoblastic leukemia

“…One could argue that differences between populations might lead to different ETV6-RUNX1 frequencies in the healthy population. Population differences have been identified for some tumor entities, including ETV6-RUNX1 + and TCF3-PBX1 + leukemias, the latter of which is more frequent in Latin America [51,52]. ETV6-RUNX1 is much less common in East Asians [53], Hispanics [54], and especially in Maori, where only 5.4% of pediatric ALL cases harbor this translocation [55].…”

“…The TCF3-PBX1 fusion is the product of a balanced or unbalanced t(1;19) translocation and is among the most frequent aberrations in childhood ALL. It is especially common in Latin America [51,52] and among black children [57], where as many as 11.8% of childhood ALL cases carry this fusion.…”

Analysis of common cytogenetic abnormalities in New Zealand pediatric ALL shows ethnically diverse carriage of ETV6‐RUNX1, without a corresponding difference in survival

“…19,20 The frequency of ETV6-RUNX1 among this New Zealand cohort was 22.5%, which sits within the normal range of 20-25% 19 and is comparable with what has been reported in China, 21 Italy, 22 and America. 23 Lower frequencies have been identified in Guatemala, 24 Mexico, 25 Saudi Arabia, 26 Spain, 27 Lebanon, 28 Pakistan, 10 Japan, Korea, and Taiwan 3 and higher frequencies have been identified in England 29 and Australia. 30 On examination of the New Zealand cohort, the discovery of a low and Hispanic American children with ALL.…”