Expression Pattern of HNRNPH1 and HNRNPK Genes in MPNs
Study Details
Study Description
Brief 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
| Condition or Disease | Intervention/Treatment | Phase |
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Detailed 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Myeloproliferative neoplasms Cases The myeloproliferative neoplasms Cases will be tested for expression of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) genes |
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.
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| Controls Healthy controls will be tested for expression of heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and K (HNRNPK) genes |
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.
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Outcome Measures
Primary Outcome Measures
- Expression of Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and Heterogeneous nuclear ribonucleoprotein K (HNRNPK) genes in myeloproliferative neoplasms (MPNs) [two years]
Expression levels of Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1) and Heterogeneous nuclear ribonucleoprotein K (HNRNPK) genes for diagnosis of myeloproliferative neoplasms.
Secondary Outcome Measures
- Correlation between expression levels of HNRNPH1 and HNRNPK genes and molecular diagnostic tests for myeloproliferative neoplasms [Two years]
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
Eligibility Criteria
Criteria
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:
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Other malignancies.
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Patients on chemotherapy or radiotherapy.
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Autoimmune diseases.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assiut University
Investigators
- Principal Investigator: Alaa Elminshawy, MD, Mac, Assiut University
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- HNRNPH1 & HNRNPK in MPNs