Transcriptomic signature can distinguish chronic neutrophilic leukemia from ambiguous neutrophilic leukemias

Chao Guo ^* Zhen-Ling Li

• China-Japan Friendship Hospital, Beijing, China

The identification of uncommon neutrophilic leukemias presents a challenging task, owing to the analogous morphological characteristics and the dearth of molecular markers.Transcriptomic profile of bone marrow cells in this disease subset has been rarely explored.The OHSU-CNL dataset, encompassing clinical parameters and parallel transcriptomic matrix, was downloaded from the GDC database. Utilizing R software, distinctive coexpressed gene modules and pivotal genes for CNL were identified. Subsequently, a diagnostic model for CNL, denoted as CNL-5, was formulated employing LASSO regression analysis. Diagnostic power of the CNL-5 model was compared with conventional clinical/genetic markers via multi-ROC analysis.Divergence of overall survival between CNL-5 risk groups was delineated by Kaplan-Meier analysis, predictive power (AUC and Harrison's C index) was obtained by time dependent ROC as well.Moreover, cell signaling pathways associating with CNL-5 risk were identified by GESA.Neither clinical indicators nor genetic markers were sufficient to classify neutrophilic leukemias. Through WGCNA, the 'brown' module was discerned to be CNL-specific (p = 8e-16, R² = 0.5). Via LASSO analysis, CNL-5 model, with risk scores based on weighted expression value of five genes (PDCD7/CR2/ZSCAN20/TRIM68/LILRA6), dichotomized patients into "CNL-like" and "Atypical-CNL" groups. Compared to Atypical-CNL group, CNL-like group demonstrated a clinical phenotype more consistent with CNL and had a significantly higher prevalence of CSF3R mutations (p < 0.05). Additionally, AUC of the CNL-5 risk model surpassed that of conventional clinical/genetic markers, which was validated by GSE42731 dataset. Poorer survival was revealed in high-risk group than that of low-risk group defined by CNL-5 model. GSEA identified CNL-5-associated pathways, including the inhibition of oxidative phosphorylation, and the activation of IL6-JAK-STAT3 signaling, etc.A novel diagnostic assessment for CNL was developed according to expression signature, exhibiting superior diagnostic utility compared to conventional indicators.