Researchers Identify Novel Biomarker, Therapeutic Target for Polycythemia Vera

The data set included 177 samples from polycythemia vera, essential thrombocytopenia, primary myelofibrosis, and healthy donors, from which the researchers found that MAPK14 was overexpressed in PV samples and was associated with more symptoms and worse outcomes.

Study findings are offering new insights into potential biomarkers and therapeutic targets for polycythemia vera (PV) treatment. Published in the Journal of Translational Medicine, the study used weighted gene co-expression network analysis to identify co-expression modules and marker mRNAs correlating with PV.

The data set included 177 samples from PV, essential thrombocytopenia (ET), primary myelofibrosis (PMF), and healthy donors, from which the researchers found that MAPK14 was overexpressed in PV samples and was associated with more symptoms and worse outcomes.

“Clinical variables were compared in MAPK14-high and MAPK14-low groups. The JAK2 mutation burden was insignificantly higher in the MAPK14-high group compared with the MAPK14-low group (90.5% vs 78.9%; P = .19), which may be due to insufficient samples,” explained the researchers. “Moreover, in comparison with the MAPK14-low group, the MAPK14-high group had significantly inferior clinical outcomes.”

Adverse clinical outcomes associated with MAPK14 overexpression included splenectomy, thrombosis, disease aggressiveness, and inferior survival.

The researchers also utilized external datasets, which confirmed that MAPK14 was expressed at a significantly higher rate in PV samples than in other myeloproliferative neoplasms (MPNs) and healthy samples, and MAPK14 overexpression in PV occurred regardless of whether it was in peripheral neutrophils or in bone marrow CD34+ cells.

In their study, the researcher highlight that MAPK14 expression was higher in JAK2 mutation carriers and that JAK2-homozygous mutation carriers had significantly higher expression of MAPK14 than all other mutation types.

“To further investigate the quantitative correlation of MAPK14 and JAK2/STAT genes, a global expression profile correlating with MAPK14 expression uncovered that JAK (JAK2/JAK3) and STAT (STAT1/STAT3/STAT5A/STATA5B) family genes were positively correlated with MAPK14 in MPN patients,” wrote the researchers. “To specific disease types of MPN, MAPK14 significantly positively correlated with JAK2 expression in PV and ET patients, respectively (PV: P = 2.35e−8, Pearson’s coefficient = 0.57; ET: P = .037, Pearson’s coefficient = 0.35).”

Based on this finding, the researchers explain that MAPK14 expression is correlated to not just the allogenic status of JAK2V617F mutation but also the mRNA levels of both JAK and STAT genes.

“This study identified MAPK14 as a promising disease marker,” they concluded and provided insight into therapeutic targets.

Reference

Guo C, Gao Y-Y, Ju Q-Q, et al. MAPK14 over-expression is a transcriptomic feature of polycythemia vera and correlates with adverse clinical outcomes. J Transl Med. Published online May 31, 2021. doi:10.1186/s12967-021-02913-3