Exploring the role of PARP9 expression in AML: prognostic implications and transcriptomic insights

Poly(ADP-ribose) polymerase 9 (PARP9) is an interferon-inducible PARP family member implicated in tumor cell survival, immune signalling, and poor prognosis, suggesting potential value as a biomarker and therapeutic target in cancer. Its expression pattern and clinical relevance in acute myeloid leukaemia (AML) is unclear. We investigated the expression of PARP9 in AML patient samples. We analysed transcriptomic data from TCGA-LAML, GTEx, Human Protein Atlas, DepMap, and BloodSpot to characterise PARP9 expression across cancers, hematopoietic hierarchies, and AML subgroups. Cross-cancer analysis showed significantly higher PARP9 expression in AML compared with most non-hematologic malignancies (p < 0.001). Within hematopoietic lineages, PARP9 expression was significantly high in megakaryocyte-erythroid progenitors (p < 0.05), B cells (p < 0.001), polymorphonuclear cells (p < 0.001), and monocytes (p < 0.001), with the highest expression in polymorphonuclear cells. AML samples exhibited ~ 2.4-fold higher expression of PARP9 when compared to normal tissues (p < 0.001). PARP9 high expression was found to be associated with specific FAB subtypes M0, M1, M2, M4 and M5 and in patients exhibiting intermediate and adverse cytogenetic risk profiles (p < 0.05). Additionally, patients with high PARP9 expression showed significantly poor overall survival outcomes (log-rank p = 0.035; HR 1.49, 95% CI 1.03-2.16), although PARP9 was not independently prognostic after adjustment for age and cytogenetic risk in multivariable Cox regression. Furthermore, the differential expression analysis identified 457 upregulated and 1141 downregulated genes associated with high PARP9 expression, which in silico analysis linked to immune and cancer-related pathways, including PD‑1/PD‑L1 signalling, NOD-like receptor signalling, cytokine-cytokine receptor interaction, and hematopoietic lineage. Overall, PARP9 was consistently highly expressed in AML and associated with adverse-risk categories, distinct transcriptional pathways, and poor survival outcomes, highlighting its potential as a biomarker warranting further study to validate its role in AML.

The online version contains supplementary material available at 10.1007/s13205-026-04768-1.