In September 2017, in Blood Advances, Antonio R. Lucena-Araujo from the Federal University of Pernambuco, Recife, Brazil, et al. reported results from their study which investigated the clinical significance of Brain and Acute Leukemia, Cytoplasmic (BAALC) gene in patients with Acute Promyelocytic Leukemia (APL).
In total, 221 consecutive newly diagnosed APL patients with a median age of 35.3 years (range 18.9–82.5) who were enrolled in the International Consortium Acute Promyelocytic Leukemia (IC-APL) and treated with All-Trans Retinoic Acid (ATRA) and anthracycline–based therapy were included in this study. BAALC gene expression was measured in Bone Marrow (BM) samples of patients using Real Time Polymerase Chain Reaction (RT-PCR).
Compared to healthy controls and other subtypes of Acute Myeloid Leukemia (AML) including Core Binding Factor AML (CBF-AML), Cytogenetically Normal AML (CN-AML) and AML Not Otherwise Specified (AML-NOS), BAALC gene expression was significantly lower in APL patients. APL Patients were then divided into two groups based on the median value of BAACL expression including low (< 1.54 [n = 110]) and high (≥ 1.54 [n = 111]) BAALC expression.
The key findings of the study were:
- 5-year Overall Survival (OS) in patients with low and high BAALC expression; 82% vs 73%, P = 0.077
- 5-year Disease Free Survival (DFS) in patients with low and high BAALC expression; 95% vs 78%, P = 0.009
- Cumulative Incidence of Relapse (CIR) in patients with low and high BAALC expression; 5% vs 21%, P = 0.01
- Early mortality rate was significantly higher in patients with high BAALC expression compared to patients with low BAALC expression; 17% vs 8%, P = 0.046
- In high-risk APL patients, 5-year DFS was significantly shorter in patients with high BAACL expression compared to patients with low BAACL expression; 53% vs 90%, P = 0.019
The key limitations of this study included the lack of validation in an independent cohort and small sample size. However, the authors concluded by suggesting that “BAALC expression could be useful in refining the risk stratification in APL” which could aid the clinical decisions on “consolidation strategies and also provide the possibility of early intervention if molecular relapse occurs”.
Although overexpression of the brain and acute leukemia, cytoplasmic (BAALC) gene is associated with primary resistant disease and shorter relapse-free, disease-free, and overall survival in different subsets of acute myeloid leukemia (AML), little is known about its clinical impact in acute promyelocytic leukemia (APL). Using real-time reverse transcriptase polymerase chain reaction, we showed that BAALC expression is significantly lower in APL compared with other subsets of AML (P < .001). We also demonstrated that BAALC overexpression was associated with shorter disease-free survival (DFS) (hazard ratio [HR], 4.43; 95% confidence interval [CI], 1.29-15.2; P = .018) in 221 consecutive patients (median age, 35 years; range, 18-82 years) with newly diagnosed APL homogeneously treated with all-trans retinoic acid and anthracycline-based chemotherapy. Cox proportional hazard modeling showed that BAALC overexpression was independently associated with shorter DFS in the total cohort (HR, 5.26; 95% CI, 1.52-18.2; P = .009) and in patients with high-risk disease (ie, those with initial leukocyte counts >10 × 109/L) (HR, 5.3; 95% CI, 1.14-24.5; P = .033). We conclude that BAALC expression could be useful for refining risk stratification in APL, although this needs to be confirmed in independent cohorts.