Clinical Characteristics and Prognostic Significance of PWWP2B Expression in AML Patients Treated with Intensive Chemotherapy

Background/Aim

PWWP domain containing 2b (PWWP2B) is a nuclear protein, which was reported to participate in the regulation of histone acetylation and chromatin modifying by forming complex with histone deacetylases (HDAC) proteins. HDACs are known to involve in chromatin remodeling. Abnormal HDACs functions may contribute to the leukemogenesis of acute myeloid leukemia (AML). Therefore, this study aimed to investigate the prognostic significance of PWWP2B expression in AML patients.

Methods

A total of 475 adult patients with newly diagnosed de novo non-M3 AML at the National Taiwan University Hospital, treated with intensive chemotherapy, were consecutively enrolled. PWWP2B expression level was detected by RNA sequencing assay. Maximally selected rank statistics were employed to find the optimal cutoff point for PWWP2B expression in survival analysis. Survival analyses were performed using the Kaplan-Meier model and the Cox proportional hazards model was used for multivariable analysis. Bioinformatics approaches for biological inference was conducted by Ingenuity Pathway Analysis.

Results

The ELN-2022 risk stratification of our AML patient cohort was as follows: 40.6% (n=193) classified as favorable, 28.2% (n=134) as intermediate, and 31.2% (n=148) as adverse. Higher PWWP2B expression was observed in AML patients compared to healthy donors (p<0.001). There is no significant difference in ELN-2022 risk stratification, age, initial leukocyte count, or gender between patients with higher and lower PWWP2B expression levels. Patients with higher PWWP2B expression had higher frequency of concurrent FLT3-ITD and SRSF2 mutation, but lower frequency of NRAS mutations. In terms of treatment outcome, AML patients with higher PWWP2B expression had a worse overall survival (OS) and relapse-free survival (RFS) compared to AML patient with lower expression (P <0.001 for OS and 0.003 for RFS). In multivariate analysis, higher PWWP2B expression level remained an independent adverse prognostic factor for both OS (HR 1.753, p<0.001) and RFS (HR 1.658, p=0.005) irrespective of age, ELN-2022, and leukocyte count at diagnosis. Intriguingly, allogeneic transplantation may overcome the poor prognosis associated with higher PWWP2B expression in AML.

Conclusions

We found that PWWP2B expression has prognostic significance in de novo AML patient treated with intensive chemotherapy. Higher PWWP2B expression is associated with worse survival outcomes. These findings suggest further investigation of HDAC targeted therapy in AML patient with high PWWP2B expression.

No relevant conflicts of interest to declare.