Association between early risk factors and CDKN2A/B deletion in pediatric patients with acute lymphoblastic leukemia in a pediatric cancer center in Colombia

Martinez, Cindy; Yunis, Luz Karime; Cabrera, E Gómez; García, Johnny; Uribe, Gloria; Quintero, Edna; Yunis, Juan J.; Ballesteros, Adriana Linares; Sarmiento, Iván

doi:10.1016/j.phoj.2022.03.001

Cited by 2 publications

(3 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(31.7%) in Mexican patients ( 38 ). Lower frequencies have also been reported in other Latin American and Asian populations, including Colombia (25%) ( 56 ), Brazil (31.8%) ( 39 ), China (20.2%) ( 15 ), and India (19.8%) ( 57 ). In our study, CDKN2A/2B DEL was associated with higher blast counts at diagnosis and high-risk features.…”

Section: Discussionmentioning

confidence: 82%

IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia

Garcia-Solorio,

Núñez-Enriquez,

Jiménez-Olivares

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

BackgroundRecurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, prognosis, and treatment selection. IKZF1plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5, CDKN2A/2B, or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B, and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL.MethodsA total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation.ResultsWe identified the IKZF1plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age (p=0.04), a trend toward high-risk stratification (p=0.06), and a decrease in 5-year Overall Survival (OS) (p=0.009) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1MUT group was older at diagnosis (p=0.0002), and most of them were classified as high-risk (73.8%, p=0.02), while patients with CDKN2A/2BMUT had a higher leukocyte count (p=0.01) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05) than the non-mutated patients. A decrease in OS was found in IKZF1MUT and CDKN2A/2BMUT patients, but the significance was lost after IKZF1plus was removed.DiscussionOur findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.

show abstract

Section: Discussionmentioning

confidence: 82%

IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia

Garcia-Solorio,

Núñez-Enriquez,

Jiménez-Olivares

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…In the field of oncology, researchers have discovered important genetic alterations. One example is the t ( Ruan et al, 2020 ; Martinez et al, 2022 ) BCR-ABL1 fusion, which is often found in cases of acute lymphoblastic leukemia (ALL) in children. Another example is the t ( Laetsch et al, 2021 ; Martinez et al, 2022 ) EWSR1-FLI1 fusion, which is frequently linked to Ewing sarcoma.…”

Section: Introductionmentioning

confidence: 99%

“…One example is the t ( Ruan et al, 2020 ; Martinez et al, 2022 ) BCR-ABL1 fusion, which is often found in cases of acute lymphoblastic leukemia (ALL) in children. Another example is the t ( Laetsch et al, 2021 ; Martinez et al, 2022 ) EWSR1-FLI1 fusion, which is frequently linked to Ewing sarcoma. These specific chromosomal translocations play a vital role in the development of these types of cancers ( Sole et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Moaveni,

Amiri,

Shademan

et al. 2024

Front. Mol. Biosci.

View full text Add to dashboard Cite

Pediatric cancers represent a tragic but also promising area for gene therapy. Although conventional treatments have improved survival rates, there is still a need for targeted and less toxic interventions. This article critically analyzes recent advances in gene therapy for pediatric malignancies and discusses the challenges that remain. We explore the innovative vectors and delivery systems that have emerged, such as adeno-associated viruses and non-viral platforms, which show promise in addressing the unique pathophysiology of pediatric tumors. Specifically, we examine the field of chimeric antigen receptor (CAR) T-cell therapies and their adaptation for solid tumors, which historically have been more challenging to treat than hematologic malignancies. We also discuss the genetic and epigenetic complexities inherent to pediatric cancers, such as tumor heterogeneity and the dynamic tumor microenvironment, which pose significant hurdles for gene therapy. Ethical considerations specific to pediatric populations, including consent and long-term follow-up, are also analyzed. Additionally, we scrutinize the translation of research from preclinical models that often fail to mimic pediatric cancer biology to the regulatory landscapes that can either support or hinder innovation. In summary, this article provides an up-to-date overview of gene therapy in pediatric oncology, highlighting both the rapid scientific progress and the substantial obstacles that need to be addressed. Through this lens, we propose a roadmap for future research that prioritizes the safety, efficacy, and complex ethical considerations involved in treating pediatric patients. Our ultimate goal is to move from incremental advancements to transformative therapies.

show abstract

Association between early risk factors and CDKN2A/B deletion in pediatric patients with acute lymphoblastic leukemia in a pediatric cancer center in Colombia

Cited by 2 publications

References 6 publications

IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia

IKZF1plus is a frequent biomarker of adverse prognosis in Mexican pediatric patients with B-acute lymphoblastic leukemia

Advances and challenges in gene therapy strategies for pediatric cancer: a comprehensive update

Contact Info

Product

Resources

About