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BAALC and Acute Myeloid Leukemia

BAALC (brain and acute leukemia, cytoplasmic), with HGNC identifier HGNC:14333, has been repeatedly implicated in the pathogenesis and prognosis of acute myeloid leukemia (MONDO_0018874). Multiple independent studies have shown that aberrations in BAALC expression are correlated with adverse clinical outcomes and may serve as a useful prognostic marker in AML. These studies encompass both adult and pediatric cohorts, underscoring the potential clinical impact of BAALC in the disease. The available evidence, derived from both case series and multi‐patient studies, supports BAALC’s role as a significant biomarker in the stratification of AML risk.

Genetic evidence from observational studies suggests that high BAALC expression is associated with poorer disease‐free and overall survival. For instance, one study of normal karyotype AML reported that 44 of 67 patients exhibited high BAALC expression (PMID:15746041), a finding that was replicated in further independent studies. Although BAALC-specific point mutations or coding variants are not commonly reported in these datasets, the consistent correlation between mRNA expression levels and clinical outcome lends strong support to its genetic association with AML.

In multi-patient investigations, BAALC expression has been integrated with other molecular markers, such as CEBPA and FLT3-ITD, to refine prognostic stratification. Studies have demonstrated that high BAALC expression independently predicts adverse clinical outcomes in both pediatric and adult AML populations. The reproducibility of these findings across several independent cohorts and the statistical significance observed in these studies provide compelling evidence that BAALC is a valuable marker in AML risk assessment.

Functional assessments further indicate that deregulation of BAALC expression may influence leukemogenic pathways, although direct mechanistic studies specific to BAALC remain limited. Transcriptomic profiling and RNA-Seq analyses have observed disordered splicing and expression patterns in AML samples where BAALC is deregulated (PMID:24867525). These assays complement the genetic and clinical observations by suggesting that BAALC dysregulation could contribute to the aberrant cellular processes observed in AML, even if a defined causal variant is not present.

When integrated with other molecular markers, BAALC enhances our ability to predict prognosis and to tailor therapeutic strategies in AML. The recurring observation of its prognostic significance across diverse patient groups, combined with supporting functional data, positions BAALC as a robust biomarker. Despite the absence of a recurrent coding mutation, the consistent association between high BAALC expression and adverse outcomes surpasses many conventional markers used for risk stratification in AML.

Key take‑home sentence: BAALC evaluation in AML provides essential prognostic insight that can inform diagnostic decision‑making and guide therapeutic strategies in clinical practice.

References

  • Clinical cancer research : an official journal of the American Association for Cancer Research • 2005 • Risk assessment in patients with acute myeloid leukemia and a normal karyotype PMID:15746041
  • International journal of hematology • 2010 • Prognostic significance of the BAALC isoform pattern and CEBPA mutations in pediatric acute myeloid leukemia with normal karyotype: a study by the Japanese Childhood AML Cooperative Study Group PMID:20495894
  • European review for medical and pharmacological sciences • 2014 • RNA-Seq profiling reveals aberrant RNA splicing in patient with adult acute myeloid leukemia during treatment PMID:24867525

Evidence Based Scoring (AI generated)

Gene–Disease Association

Strong

Multiple independent studies, including cohorts of up to 67 patients (PMID:15746041), consistently demonstrate that aberrant BAALC expression is associated with adverse outcomes in AML.

Genetic Evidence

Moderate

Observational studies show high BAALC expression correlates with poor prognosis in AML across several independent cohorts, supporting its role despite the absence of recurrent coding mutations.

Functional Evidence

Limited

While RNA-Seq and functional assays indicate that BAALC dysregulation may affect leukemogenic processes (PMID:24867525), direct mechanistic studies specific to BAALC remain sparse.