Poor Prognosis Biomolecular Factors Are Highly Frequent in Childhood Acute Leukemias From Oaxaca, Mexico

Abstract

<jats:sec><jats:title>Objective:</jats:title><jats:p> To investigate the cellular and molecular epidemiology of acute leukemias in vulnerable populations of children and adolescents in Oaxaca de Juarez, Mexico. </jats:p></jats:sec><jats:sec><jats:title>Material and Methods:</jats:title><jats:p> Descriptive, cross-sectional and retrospective study, conducted from 2014 to 2018 in which profiles of molecular and immunophenotypic aberrations were investigated in children and adolescents diagnosed with acute leukemia, by evaluating 28 molecular abnormalities by HemaVision-Q28 multiplex RT-PCR kit and standardized EuroFlow Immunophenotyping of bone marrow cells. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> We included 218 patients, with 82.5% younger than 14 years and 17.5% adolescents. The median age was 9 years and a main peak of incidence was recorded at age of 4 to 5 years. B-cell acute lymphoblastic leukemia was diagnosed in 70.64% of all cases, acute myeloid leukemia was in 22.48%, T-cell acute lymphoblastic leukemia in 6.42%, and mixed lineage acute leukemia in 0.46% of cases. Overall, chromosomal translocations were positive in 29.82% of cases. While 65.31% of patients with acute myeloid leukemia reported aberrancies, only in 18.83% of B-cell acute lymphoblastic leukemia cases genetic abnormalities were obvious. Surprisingly, most prevalent translocations in B-cell acute lymphoblastic leukemia were t(9;22) in 20.7%, followed by t(4;11) in 17.2% and t(6;11) in 13.8%, whereas patients with acute myeloid leukemia showed t(15;17) in 40.6% and t(8;21) in 21.9%. In contrast, an homogeneous expression of t(3;21) and t(6;11) was recorded for T-cell acute lymphoblastic leukemia and mixed lineage acute leukemia cases, respectively. Except for t(1;19), expressed only by pre-B cells, there was no association of any of the studied translocations with differentiation stages of the B-leukemic developmental pathway. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Our findings identify near 50% of patients with acute lymphoblastic leukemia at debut with high-risk translocations and poor prognosis in B-cell acute lymphoblastic leukemia as well as an unexpected increase of acute myeloid leukemia cases in young children, suggesting a molecular shift that support a higher incidence of poor prognosis cases in Oaxaca. </jats:p></jats:sec>

Low Prevalence of ETV6::RUNX1 Fusion Gene in a Hispanic Population

“…For this purpose, we used the TaqMan one-step RT-qPCR method toentify the prevalence of the ETV6::RUNX1 (10.5%), TCF3::PBX1 (7.7%), KMT2A::AFF1 (2.8%), and BCR::ABL1p 190 (3.6%) fusion genes and their association with early mortality in patients with B- ALL. The overall prevalence was 24.2%, which was relatively higher than in previous studies carried out by our research group (17.7%) ( 18 ), and 18.83% in a study performed in southern Mexico ( 20 ). Also, we detected a higher average age of 8.6 years (range.2–17.7 years) than that of Caucasian children with ALL (5.4) ( 28 ), similar to a recent study in Mexico, which is 9.3 (< 1–19, N = 154, 2020 B-ALL ( 20 ).…”

“…The overall prevalence was 24.2%, which was relatively higher than in previous studies carried out by our research group (17.7%) ( 18 ), and 18.83% in a study performed in southern Mexico ( 20 ). Also, we detected a higher average age of 8.6 years (range.2–17.7 years) than that of Caucasian children with ALL (5.4) ( 28 ), similar to a recent study in Mexico, which is 9.3 (< 1–19, N = 154, 2020 B-ALL ( 20 ). This increase is the result of a higher percentage in the cohort of patients with ALL over 10 years of age (39.7%) ( Table 1 ) related to the increase reported on ALL in the Latin American population ( 5 ).…”

Development and Validation of a One-Step RT-qPCR Assay for Identifying Common Fusion Gene Transcripts Associated with the Prognosis of Mexican Children with B-Lineage Acute Lymphoblastic Leukemia

“…It was present at all ages but most commonly observed in children under 10 years of age (Table 2). The low prevalence of ETV6-RUNX1 is consistent with previous Mexican reports using different detection methodologies: 8.7% [27], 8.5% [28], 7.4% [22], 6.9% [23], 13.5% [19], and 14.9% [29]. These results are similar to those reported in Hispanics living in other countries 4.5% in Guatemalan and 14% in Hispanic residing in the Northern California [30,31].…”

“…The frequencies of ETV6-RUNX1, TCF3-PBX1, KMT2A-AFF1 and BCR-ABL1p190 were 10.3%, 7.5%, 2.8% and 3.6%, respectively, similar to a previous study conducted by our research group where a comparable number of clinical samples were analyzed [22]. Of note, the prevalence of these four fusion gene transcripts was 24.2%, which is similar to the 20% detection reported in a recent study carried out in southern Mexico using an in vitro diagnostic test (HemaVision-Q28, DNA Diagnostic) [23]. Nonetheless, it has a low prevalence compared with studies conducted in other countries, particularly developed nations [24,25].…”

Patient-Derived Bone Marrow Spheroids Reveal Leukemia-Initiating Cells Supported by Mesenchymal Hypoxic Niches in Pediatric B-ALL

“…93.5% of poor prognosis cases of pediatric leukemias are registered in low- to middle-income countries, where 90% of the world’s children live, with relapses occurring at very early stages of treatment and increasing numbers of high-risk fates ( 1 , 2 , 32 ). Such epidemiology highlights the importance of a comprehensive understanding of the origins and coevolution of the disease in the context of micro/macroenvironmental cues.…”