Expression pattern of heterogeneous nuclear ribonucleoprotein H1 and heterogeneous nuclear ribonucleoprotein K in Myeloproliferative neoplasms

Background
Self-renewing hematopoietic stem cells differentiate into myeloid or lymphoid lineages. Myeloproliferative neoplasms (MPNs) are a group of disorders characterized by aberrant proliferation of one or more terminal myeloid cell lines. They include chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia, and primary myelofibrosis, along with chronic neutrophilic leukemia, chronic eosinophilic leukemia, and unclassifiable MPNs, as recognized by the WHO classification (2022).
Heterogeneous nuclear ribonucleoproteins (hnRNPs), a family of RNA-binding proteins, regulate gene expression and have been implicated in hematologic malignancies. Downregulation of heterogeneous nuclear ribonucleoprotein K (HNRNPK) promotes MPN growth in vivo, while its overexpression has been associated with accelerated CML progression, suggesting a potential prognostic and therapeutic role. Similarly, heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1), one of the earliest identified RNA-binding proteins, contributes to RNA stabilization, editing, and modification. Overexpression of HNRNPH1 promotes carcinogenesis by upregulating oncogenes and suppressing tumor-suppressor genes, including P53, Ron, and BCL-X.


Patients and methods
A cross-sectional study was conducted on 150 participants: 120 newly diagnosed MPN patients and 30 healthy controls. HNRNPH1 and HNRNPK gene expression were measured using reverse transcription-quantitative PCR, and protein levels were assessed via western blotting.


Results

HNRNPH1 mRNA was significantly downregulated in MPNs versus controls (
P
<0.001), while HNRNPK protein was overall reduced (
P
=0.028) but varied by subtype, lowest in CML and highest in essential thrombocythemia (
P
<0.001). JAK2 mutations were associated with lower HNRNPH1 (
P
=0.001), HNRNPK mRNA (
P
<0.001), and HNRNPK protein (
P
=0.049), correlating negatively with HNRNPK mRNA (
r
=–0.643), HNRNPH1 mRNA (
r
=–0.340), and HNRNPK protein (
r
=–0.212). Receiver operating characteristic analysis showed moderate diagnostic accuracy for HNRNPK protein (area under curve 0.630) and higher for HNRNPH1 mRNA (area under curve 0.743).



Conclusion
HNRNPH1 and HNRNPK exhibit distinct gene–protein expression patterns in MPNs, indicating post-transcriptional regulation and show potential value as confirmatory diagnostic markers, while HNRNPK may hold prognostic value in myelofibrosis.