Expression Pattern of HNRNPH1 and HNRNPK Genes in MPNs

Myeloproliferative Neoplasms (MPNs) Clinical Trial

Official title:

Expression Pattern of Heterogeneous Nuclear Ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) Genes in Myeloproliferative Neoplasms

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05782985
• Other study ID #: HNRNPH1 & HNRNPK in MPNs
• Status: Recruiting
• Start date: March 20, 2023
• Est. completion date: June 1, 2025

Study information

• Verified date: July 2023
• Source: Assiut University
• Contact: Alaa Elminshawy, MD, MSc
• Phone: 01128892117
• Email: alaa.elminshawy[@]med.aun.edu.eg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of the study is to evaluate the expression pattern of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) genes in Myeloproliferative neoplasms as a possible indicator of disease progression and as a potential therapeutic target

Description:

Self-renewing Hematopoietic pluripotent stem cells can develop into either myeloid or lymphoid lineages. A diverse range of diseases known as myeloproliferative neoplasms (MPNs) develop due to the aberrant proliferation of one or more terminal myeloid cell lines in the peripheral circulation. MPNs come in four traditional forms: chronic myeloid leukaemia (CML), polycythaemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Chronic neutrophilic leukaemia (CNL), chronic eosinophilic leukaemia (CEL), and MPN unclassifiable, were also included in the WHO classification. While PV, ET, and PMF are BCR-ABL1 negative, CML is BCR-ABL1 positive.

In eukaryotic cell's nucleus, many ribonucleoproteins (RNPs) assemble on to recently produced transcripts. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are one type of RNPs. Some hnRNPs are now known to play a role in the development of human hematologic malignancies. Disease research is becoming more interested in how hnRNPs control gene expression. Numerous cancers exhibit changed hnRNPs expression levels, which raises the possibility that they play a part in carcinogenesis.

For instance, leukaemia cells showed downregulation of Heterogeneous nuclear ribonucleoprotein K (HNRNPK). In vivo myeloproliferative neoplasm tumour growth was accelerated by HNRNPK knockdown. On the other hand, A study suggests that HNRNPK overexpression could accelerate CML development and thus a possible indicator of CML progression and a potential therapeutic target might be HNRNPK.

Moreover, one of the earliest RNA-binding proteins (RBPs) to be identified, Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) contributes to RNA stabilization, RNA editing, and RNA modification. Previous research has demonstrated that high levels of HNRNPH1 expression leads to carcinogenesis by both upregulating the expression of oncogenes and downregulating the expression of tumour suppressor genes such P53, Ron, and BCL-X.

The investigators performed the study with the aim to study the expression level of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) genes and their proteins in MPNs and to investigate the association of HNRNPH1 and HNRNPK with molecular diagnostic tests of MPNs.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: June 1, 2025
• Est. primary completion date: March 20, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

The study will be carried out on patients newly diagnosed with one of the myeloproliferative neoplasms based on WHO Criteria for diagnosis of MPNs whether males or females and of any age.

Exclusion Criteria:

• Other malignancies.

• Patients on chemotherapy or radiotherapy.

• Autoimmune diseases.

Related Conditions & MeSH terms

• Myeloproliferative Disorders
• Myeloproliferative Neoplasms (MPNs)
• Neoplasms

Intervention

Diagnostic Test:
• Reverse transcription-quantitative polymerase chain reaction (RT-qPCR)
Blood samples from the myeloproliferative neoplasms cases and the controls will be tested with Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for expression of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) genes.

Locations

Country	Name	City	State
Egypt	Assiut University Department of Clinical Pathology	Assiut

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (10)

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. doi: 10.1182/blood-2016-03-643544. Epub 2016 Apr 11. — View Citation

Braun S, Enculescu M, Setty ST, Cortes-Lopez M, de Almeida BP, Sutandy FXR, Schulz L, Busch A, Seiler M, Ebersberger S, Barbosa-Morais NL, Legewie S, Konig J, Zarnack K. Decoding a cancer-relevant splicing decision in the RON proto-oncogene using high-throughput mutagenesis. Nat Commun. 2018 Aug 17;9(1):3315. doi: 10.1038/s41467-018-05748-7. — View Citation

Decorsiere A, Cayrel A, Vagner S, Millevoi S. Essential role for the interaction between hnRNP H/F and a G quadruplex in maintaining p53 pre-mRNA 3'-end processing and function during DNA damage. Genes Dev. 2011 Feb 1;25(3):220-5. doi: 10.1101/gad.607011. — View Citation

Dreyfuss G, Matunis MJ, Pinol-Roma S, Burd CG. hnRNP proteins and the biogenesis of mRNA. Annu Rev Biochem. 1993;62:289-321. doi: 10.1146/annurev.bi.62.070193.001445. No abstract available. — View Citation

Du Q, Wang L, Zhu H, Zhang S, Xu L, Zheng W, Liu X. The role of heterogeneous nuclear ribonucleoprotein K in the progression of chronic myeloid leukemia. Med Oncol. 2010 Sep;27(3):673-9. doi: 10.1007/s12032-009-9267-z. Epub 2009 Aug 4. — View Citation

Gallardo M, Lee HJ, Zhang X, Bueso-Ramos C, Pageon LR, McArthur M, Multani A, Nazha A, Manshouri T, Parker-Thornburg J, Rapado I, Quintas-Cardama A, Kornblau SM, Martinez-Lopez J, Post SM. hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies. Cancer Cell. 2015 Oct 12;28(4):486-499. doi: 10.1016/j.ccell.2015.09.001. Epub 2015 Sep 24. — View Citation

Garneau D, Revil T, Fisette JF, Chabot B. Heterogeneous nuclear ribonucleoprotein F/H proteins modulate the alternative splicing of the apoptotic mediator Bcl-x. J Biol Chem. 2005 Jun 17;280(24):22641-50. doi: 10.1074/jbc.M501070200. Epub 2005 Apr 18. — View Citation

Han SP, Tang YH, Smith R. Functional diversity of the hnRNPs: past, present and perspectives. Biochem J. 2010 Sep 15;430(3):379-92. doi: 10.1042/BJ20100396. — View Citation

Panelli D, Lorusso FP, Papa F, Panelli P, Stella A, Caputi M, Sardanelli AM, Papa S. The mechanism of alternative splicing of the X-linked NDUFB11 gene of the respiratory chain complex I, impact of rotenone treatment in neuroblastoma cells. Biochim Biophys Acta. 2013 Feb;1829(2):211-8. doi: 10.1016/j.bbagrm.2012.12.001. Epub 2012 Dec 12. — View Citation

Tefferi A, Thiele J, Vardiman JW. The 2008 World Health Organization classification system for myeloproliferative neoplasms: order out of chaos. Cancer. 2009 Sep 1;115(17):3842-7. doi: 10.1002/cncr.24440. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Expression of Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and Heterogeneous nuclear ribonucleoprotein K (HNRNPK) genes in myeloproliferative neoplasms (MPNs)	Expression levels of Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and Heterogeneous nuclear ribonucleoprotein K (HNRNPK) genes for diagnosis of myeloproliferative neoplasms.	two years
Secondary	Correlation between expression levels of HNRNPH1 and HNRNPK genes and molecular diagnostic tests for myeloproliferative neoplasms	Correlation between expression levels of HNRNPH1 and HNRNPK genes and molecular diagnostic tests for myeloproliferative neoplasms as Philadelphia chromosome or JAK2 V617F or JAK2 exon 12 mutation or CALR or MPL mutation according to the case	Two years