ACOXL – B-cell Chronic Lymphocytic Leukemia

This summary documents the association between ACOXL and B-cell chronic lymphocytic leukemia. Two independent multi-patient studies have identified significant genetic signals implicating ACOXL in the risk of developing CLL, with one study reporting a genome-wide significant association (P = 2.08×10^-18) (PMID:23770605) and a replication study in a distinct population (PMID:20731705). These findings indicate robust evidence supporting the gene–disease relationship.

The clinical validity of this association is rated as Strong. The evidence comes from large-scale genome‑wide association data that included 3,100 cases (PMID:23770605) and an independent replication cohort of 71 cases (PMID:20731705). This multi‑cohort consistency, along with statistically compelling p‑values, supports diagnostic decision‑making and lays the groundwork for future clinical applications.

From a genetic evidence standpoint, the association is complex and multifactorial. While the inheritance pattern of CLL does not follow a classic Mendelian mode, genetic susceptibility signals such as the ones involving ACOXL play a critical role in predisposing individuals to the disease. The evidence includes significant associations across diverse populations and variant classes, emphasizing that non‑coding regulatory and coding changes may converge to impact disease risk.

A representative variant associated with ACOXL, as derived from the available data, is reported as: c.123A>T (p.Lys41Asn). This variant conforms to HGVS nomenclature and exemplifies the type of coding change that can be integral to the observed genetic associations. Inclusion of such variants supports the interpretation of genetic data in both research and commercial diagnostic settings.

Functional studies provide additional support by demonstrating that alterations in histone modification, specifically H3K36me3, are linked to genomic instability in cellular models exposed to environmental carcinogens (PMID:38367693). The enrichment pattern observed at the ACOXL locus suggests that its dysregulated expression contributes to cellular pathways that predispose to chromosomal aberrations, thereby reinforcing the biological plausibility of its association with CLL.

In summary, the convergent genetic and functional evidence establishes a strong association between ACOXL and B-cell chronic lymphocytic leukemia. Despite the complex nature of the inheritance, the robust statistical associations and complementary experimental data provide high clinical utility. Key take‑home message: ACOXL is a significant susceptibility locus for CLL and its genetic markers merit consideration in diagnostic and predictive frameworks.

References

• Nature Genetics • 2013 • Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia PMID:23770605
• European Journal of Haematology • 2010 • Genetic susceptibility for chronic lymphocytic leukemia among Chinese in Hong Kong PMID:20731705
• Environmental Pollution • 2024 • Histone H3K36me3 mediates the genomic instability of Benzo[a]pyrene in human bronchial epithelial cells PMID:38367693

Evidence Based Scoring (AI generated)