Genetic Mutations in B-Acute Lymphoblastic Leukemia Among African American and European American Children

Reddy, Amit; Espinoza, Ingrid; Cole, D. E.; Schallheim, Jason; Poosarla, Teja; Bhanat, Eldrin; Zhou, Yunyun; Zabaleta, Jovanny; Megason, Gail; Gómez, Christian R.

doi:10.1016/j.clml.2018.08.003

Cited by 4 publications

(3 citation statements)

References 32 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, Chow et al (2010) discussed that although Black children have a 28% decreased risk for ALL (odds ratio = 0.72; confidence interval [0.65, 0.80]) compared with White and Hispanic children, there may be genetic (tumor and germline DNA) as well as environmental factors that increase their susceptibility to cancer. In addition, in epidemiologic studies of children with leukemia, unfavorable disease-specific characteristics were observed more in diverse racial/ethnic groups compared with White, non-Hispanics children (Aldrich et al, 2006;Njoku et al, 2013) and these unfavorable characteristics in the biology of the leukemia and/or genetic aberrations may contribute to disparities in OS for children with ALL (Linabery & Ross, 2008;Lohmueller et al, 2008;Reddy et al, 2018). This suggests that utilization of risk-adapted cancer treatments in Black children with ALL may be critical for OS (Dippenaar et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

A Literature Review of Racial Disparities in Overall Survival of Black Children With Acute Lymphoblastic Leukemia Compared With White Children With Acute Lymphoblastic Leukemia

Eche

Aronowitz

2020

J Pediatr Oncol Nurs

View full text Add to dashboard Cite

Despite major advances in acute lymphoblastic leukemia [ALL] treatment, poorer overall survival (OS) persists for Black children with ALL compared with White children with ALL. The purpose of this literature review was to examine the racial disparities on OS in Black versus White children with ALL. The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline, PubMed, and Academic Search Complete databases were searched using the Medical Subject Heading (MeSH) terms: survival or mortality or outcome AND black or African-American or AA or minority AND racial disparities or race or racial/ethnic disparities AND cancer in children or pediatric cancer or children with leukemia or children with ALL for articles published in English between January 2009 and July 2019. Exclusion criteria were non-research articles, systematic reviews, conference abstracts, editorials, commentaries, correspondence, and case reports. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, data were extracted, appraised, and synthesized. Sixteen articles met the inclusion criteria. Sample sizes across studies ranged from 184 to 31,866 participants. The factors most associated with disparities in OS included: age at diagnosis (e.g., <1 year and/or >10 years old), differences in clinical prognosticators (e.g., white blood cell count at diagnosis, T-cell vs. precursor B-cell immunophenotype, central nervous system disease status, cytogenetic profile) and lower socioeconomic status. Future prospective studies are needed to elucidate the role of these factors in OS of Black children with ALL.

show abstract

Section: Discussionmentioning

confidence: 99%

A Literature Review of Racial Disparities in Overall Survival of Black Children With Acute Lymphoblastic Leukemia Compared With White Children With Acute Lymphoblastic Leukemia

Eche

Aronowitz

2020

J Pediatr Oncol Nurs

View full text Add to dashboard Cite

show abstract

“…Another study demonstrated that the survival rate of children with B-ALL was higher in European American children (EA) than in African American children (AA), which appeared to be due to the different canonical pathways affected in each case. Telomerase signaling is related to AA pathways, while chromosome aberrations in EA more frequently affect genes involved with homologous recombination [ 192 ]. This suggests that hTERT may have a different influence on B-ALL with regard to different populations; nonetheless, large-scale studies need to be done to verify this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia

Mota

Camargo

Biojone

et al. 2023

Genes

View full text Add to dashboard Cite

Telomeres and telomerase are closely linked to uncontrolled cellular proliferation, immortalization and carcinogenesis. Telomerase has been largely studied in the context of cancer, including leukemias. Deregulation of human telomerase gene hTERT is a well-established step in leukemia development. B-acute lymphoblastic leukemia (B-ALL) recovery rates exceed 90% in children; however, the relapse rate is around 20% among treated patients, and 10% of these are still incurable. This review highlights the biological and clinical relevance of telomerase for B-ALL and the implications of its canonical and non-canonical action on signaling pathways in the context of disease and treatment. The physiological role of telomerase in lymphocytes makes the study of its biomarker potential a great challenge. Nevertheless, many works have demonstrated that high telomerase activity or hTERT expression, as well as short telomeres, correlate with poor prognosis in B-ALL. Telomerase and related proteins have been proven to be promising pharmacological targets. Likewise, combined therapy with telomerase inhibitors may turn out to be an alternative strategy for B-ALL.

show abstract

“…In recent years, the advent of microarray and next-generation sequencing (NGS) technologies, gene expression, DNA copy number, and mutation analyses has enabled the identification of many genetic abnormalities in tumor suppressors, cell cycle control genes, transcription factors and coactivators, and the genes involved in the development, proliferation, and signaling of B-cell lines. 1,3,6,7 More specifically, the use of NGS technologies in leukemia has changed the perspective of leukemia pathogenesis because it is possible to examine genetic abnormalities with massively parallel analysis and deep sequencing ability. 2,4,[7][8][9][10] In this study, mutation and expression analyses of genes considered to be genetic prognostic factors (associated with disease-free survival, overall survival time, risk of relapse, and treatment response) in independent studies were analyzed in our study group.…”

Section: Introductionmentioning

confidence: 99%

Genetic Profiling of Pediatric Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

et al. 2022

View full text Add to dashboard Cite

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous leukemia subgroup. It has multiple sub-types that are likely to be classified by prognostic factors. Following a systematic literature review, this study analyzed the genes correlated with BCP-ALL prognosis (IKZF1, PAX5, EBF1, CREBBP, CRLF2, JAK2, ERG, CXCR4, ZAP70, VLA4, NF1, NR3C1, RB1, TSLP, ZNRF1, and FOXO3A), specifically their nucleotide variations and expression profiles in pediatric BCP-ALL samples. The study included 45 pediatric BCP-ALL patients with no cytogenetic anomaly and a control group of 10 children. The selected genes' hot-spot regions were sequenced using next-generation sequencing, while Polymorphism Phenotyping v2 and Supplemental Nutrition Assistance Program were used to identify pathogenic mutations. The expression analysis was performed using quantitative real-time polymerase chain reaction. The mutation analysis detected 328 variants (28 insertions, 47 indels, 74 nucleotide variants, 75 duplications, and 104 deletions). The most and least frequently mutated genes were IKZF1 and CREBBP, respectively. There were statistically significant differences between patients and controls for mutation distribution in eight genes (ERG, CRLF2, CREBBP, TSLP, JAK2, ZAP70, FOXO3A, and NR3C1). The expression analysis revealed that JAK and ERG were significantly overexpressed in patients compared with controls (respectively, p = 0.004 and p = 0.003). This study combined genes and pathways previously analyzed in pediatric BCP-ALL into one dataset for a comprehensive analysis from the same samples to unravel candidate prognostic biomarkers. Novel mutations were identified in all of the studied genes.

show abstract

Genetic Mutations in B-Acute Lymphoblastic Leukemia Among African American and European American Children

Cited by 4 publications

References 32 publications

A Literature Review of Racial Disparities in Overall Survival of Black Children With Acute Lymphoblastic Leukemia Compared With White Children With Acute Lymphoblastic Leukemia

A Literature Review of Racial Disparities in Overall Survival of Black Children With Acute Lymphoblastic Leukemia Compared With White Children With Acute Lymphoblastic Leukemia

The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia

Genetic Profiling of Pediatric Patients with B-Cell Precursor Acute Lymphoblastic Leukemia

Contact Info

Product

Resources

About