Details of Disease

General Information of Disease (ID: DISB5FPO)

• Disease Name: Polycythemia vera
• Synonyms: PRV; primary polycythemia; polycythemia vera; Osler-Vaquez disease; proliferative polycythaemia; acquired primary erythrocytosis; PV; Vaquez disease; Osler-Vaquez syndrome; polycythemia rubra vera; polycythemia vera, somatic; polycythaemia rubra vera
• Disease Class: 2A20: Myeloproliferative neoplasm
• Definition: Polycythemia vera (PV) is an acquired myeloproliferative disorder characterized by an elevated absolute red blood cell mass caused by uncontrolled red blood cell production, frequently associated with uncontrolled white blood cell and platelet production.
• Disease Hierarchy:
  DIS8B6VW: Polycythemia
  DIS3I1DX: Erythroid neoplasm
  DISB5FPO: Polycythemia vera
• ICD Code:
  ICD-11: ICD-11: 2A20.4
  ICD-10: ICD-10: D45
• Disease Identifiers:
  MONDO ID: MONDO_0009891
  MESH ID: D011087
  UMLS CUI: C0032463
  OMIM ID: 263300
  MedGen ID: 45996
  Orphanet ID: 729
  SNOMED CT ID: 109992005

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 4 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Fedratinib	DM4ZBK6	Approved	Small molecular drug	[1]
Momelotinib	DMF98Q0	Approved	Small molecular drug	[2]
Ropeginterferon alfa-2b	DMPGVKM	Approved	NA	[3]
Uracil mustard	DMHL7OB	Approved	Small molecular drug	[4]

This Disease is Treated as An Indication in 8 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ITF2357	DMFZBNE	Phase 3	Small molecular drug	[5]
P1101	DM5DRMY	Phase 3	Small molecular drug	[6]
RG7388	DMF5GZI	Phase 3	Small molecular drug	[2]
XL019	DMJ6F5C	Phase 3	Small molecular drug	[7]
PRM-151	DMK8PTH	Phase 2	NA	[2]
PTG-300	DMOYS8A	Phase 2	Peptide	[8]
Sapablursen	DM95T5Z	Phase 2	Ligand-conjugated antisense	[9]
M012	DME6UNO	Phase 1	Small molecular drug	[10]

This Disease is Treated as An Indication in 1 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
MGN-4893	DMAMAUE	Investigative	NA	[11]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 22 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ABL1	TT6B75U	Limited	Biomarker	[12]
JAK1	TT6DM01	Limited	Biomarker	[13]
JMJD1C	TTBISK4	Limited	Biomarker	[14]
SOCS3	TTI0ME6	Disputed	Genetic Variation	[15]
ELANE	TTPLTSQ	moderate	Biomarker	[16]
ACKR1	TTKY2NS	Strong	Biomarker	[17]
BCL2L2	TTQ79W8	Strong	Biomarker	[18]
CD1A	TTBGTFN	Strong	Biomarker	[19]
CD34	TTZAVYN	Strong	Biomarker	[20]
DSG3	TTEO4P8	Strong	Biomarker	[21]
F5	TT1O264	Strong	Genetic Variation	[22]
HBB	TTM6HK1	Strong	Biomarker	[23]
HRC	TTR4FKD	Strong	Biomarker	[24]
IFNA2	TTSIUJ9	Strong	Biomarker	[25]
IL11	TTGUYTR	Strong	Altered Expression	[26]
MYB	TT8V13P	Strong	Genetic Variation	[27]
PTPN6	TT369M5	Strong	Altered Expression	[28]
SLC14A1	TTWVJU1	Strong	Genetic Variation	[29]
THPO	TTCG5PE	Strong	Genetic Variation	[30]
TICAM1	TT2GQT6	Strong	Biomarker	[31]
TYK2	TTBYWP2	Strong	Genetic Variation	[32]
SH2B3	TT36N7Z	Definitive	Genetic Variation	[33]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC14A2	DT8QC7K	Strong	Genetic Variation	[29]
SLC22A17	DTXI9E6	Strong	Genetic Variation	[34]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
AKR1C4	DEAJN47	Strong	Genetic Variation	[35]

This Disease Is Related to 39 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
HBA1	OTW2BQF4	moderate	Biomarker	[36]
IL3	OT0CQ35N	moderate	Biomarker	[37]
PRB1	OTV0SYMD	moderate	Biomarker	[38]
SOAT1	OTB4Y5RJ	moderate	Altered Expression	[39]
ACO1	OT2VUR7L	Strong	Genetic Variation	[40]
ACSL6	OT0TT8P8	Strong	Genetic Variation	[41]
ACTN2	OT9FOLD7	Strong	Biomarker	[42]
CD63	OT2UGZA9	Strong	Biomarker	[43]
CENPU	OTQ4TZRS	Strong	Biomarker	[44]
CH25H	OT9S2BSW	Strong	Biomarker	[45]
CSRP3	OTECBJMV	Strong	Biomarker	[37]
DERL1	OTJUS74N	Strong	Biomarker	[46]
EIF2S1	OTM0GDTP	Strong	Genetic Variation	[47]
ERFE	OTSES1HA	Strong	Altered Expression	[48]
FANCB	OTMZTXB5	Strong	Biomarker	[49]
FIP1L1	OTF91GTL	Strong	Biomarker	[50]
GATA1	OTX1R7O1	Strong	Biomarker	[51]
GYPB	OTESHUIX	Strong	Biomarker	[52]
GYPE	OTBHAG6A	Strong	Biomarker	[52]
HBS1L	OTA3U1N6	Strong	Genetic Variation	[27]
IFNA1	OTPMKY0L	Strong	Biomarker	[53]
INTU	OTXB13E6	Strong	Biomarker	[54]
IRAK2	OT6Y1QZN	Strong	Altered Expression	[55]
KANK1	OT2E7A6W	Strong	Genetic Variation	[56]
L3MBTL1	OT8M52QY	Strong	Biomarker	[57]
L3MBTL2	OTKX1XIX	Strong	Genetic Variation	[57]
LAMA5	OTIIXE4M	Strong	Biomarker	[58]
LIG3	OT48SKET	Strong	Altered Expression	[59]
MAVS	OTTQ0J64	Strong	Biomarker	[31]
MYOM2	OTD2UOXW	Strong	Biomarker	[60]
NECTIN1	OTTE5ZR6	Strong	Biomarker	[61]
NFIB	OTX94PD0	Strong	Biomarker	[62]
PPIP5K1	OT06HYH8	Strong	Biomarker	[31]
PRM2	OTSAXTSQ	Strong	Genetic Variation	[47]
PTPN9	OTNAR1I2	Strong	Altered Expression	[63]
PVR	OT3N91T7	Strong	Biomarker	[64]
SPRY4	OT2VK9N0	Strong	Biomarker	[65]
STAT5A	OTBSJGN3	Strong	Altered Expression	[66]
STAT5B	OTZVPEBT	Strong	Genetic Variation	[67]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 212327
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] FDA Approved Drug Products from FDA Official Website. 2021. Application Number: 761166.
• [4] Uracil mustard FDA Label
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7490).
• [6] ClinicalTrials.gov (NCT01949805) Pegylated Interferon Alpha-2b Versus Hydroxyurea in Polycythemia Vera (PROUD-PV). U.S. National Institutes of Health.
• [7] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7971).
• [8] ClinicalTrials.gov (NCT04767802) PTG-300 in Patients With Polycythemia Vera and Elevated Hematocrit. U.S. National Institutes of Health.
• [9] ClinicalTrials.gov (NCT05143957) A Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISIS 702843 Administered to Patients With Phlebotomy Dependent Polycythemia Vera (PD-PV). U.S.National Institutes of Health.
• [10] Targeting iron metabolism in drug discovery and delivery. Nat Rev Drug Discov. 2017 Jun;16(6):400-423.
• [11] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [12] Targeted molecular characterization shows differences between primary and secondary myelofibrosis.Genes Chromosomes Cancer. 2020 Jan;59(1):30-39. doi: 10.1002/gcc.22789. Epub 2019 Sep 2.
• [13] Risk factors for infections and secondary malignancies in patients with a myeloproliferative neoplasm treated with ruxolitinib: a dual-center, propensity score-matched analysis.Leuk Lymphoma. 2020 Mar;61(3):660-667. doi: 10.1080/10428194.2019.1688323. Epub 2019 Nov 12.
• [14] Epigenetic regulation of NFE2 overexpression in myeloproliferative neoplasms.Blood. 2018 May 3;131(18):2065-2073. doi: 10.1182/blood-2017-10-810622. Epub 2018 Mar 8.
• [15] A new polycythaemia vera-associated SOCS3 SH2 mutant (SOCS3F136L) cannot regulate erythropoietin responses.Br J Haematol. 2009 Nov;147(4):450-8. doi: 10.1111/j.1365-2141.2009.07860.x. Epub 2009 Sep 5.
• [16] A novel oral neutrophil elastase inhibitor (ONO-6818) inhibits human neutrophil elastase-induced emphysema in rats.Am J Respir Crit Care Med. 2002 Aug 15;166(4):496-500. doi: 10.1164/rccm.2103118.
• [17] Glycoprotein D-independent spread of pseudorabies virus infection in cultured peripheral nervous system neurons in a compartmented system.J Virol. 2007 Oct;81(19):10742-57. doi: 10.1128/JVI.00981-07. Epub 2007 Jul 25.
• [18] Activity of the BH3 mimetic ABT-737 on polycythemia vera erythroid precursor cells.Blood. 2009 Feb 12;113(7):1522-5. doi: 10.1182/blood-2008-03-143321. Epub 2008 Dec 5.
• [19] Erdheim-Chester Disease With Multiorgan Involvement, Following Polycythemia Vera: A Case Report.Medicine (Baltimore). 2016 May;95(20):e3697. doi: 10.1097/MD.0000000000003697.
• [20] Serum of myeloproliferative neoplasms stimulates hematopoietic stem and progenitor cells.PLoS One. 2018 May 31;13(5):e0197233. doi: 10.1371/journal.pone.0197233. eCollection 2018.
• [21] Keratin Retraction and Desmoglein3 Internalization Independently Contribute to Autoantibody-Induced Cell Dissociation in Pemphigus Vulgaris.Front Immunol. 2018 Apr 25;9:858. doi: 10.3389/fimmu.2018.00858. eCollection 2018.
• [22] The relationship between factor V Leiden, prothrombin G20210A, and MTHFR mutations and the first major thrombotic episode in polycythemia vera and essential thrombocythemia.Ann Hematol. 2014 Feb;93(2):203-9. doi: 10.1007/s00277-013-1838-6. Epub 2013 Jul 5.
• [23] Hemoglobin Hiroshima (beta-143 histidine--aspartic acid): a newly identified fast moving beta chain variant associated with increased oxygen affinity and compensatory erythremia.J Clin Invest. 1969 Mar;48(3):525-35. doi: 10.1172/JCI106010.
• [24] No evidence for an altered mRNA expression or protein level of haematopoietic cell phosphatase in CD34+ bone marrow progenitor cells or mature peripheral blood cells in polycythaemia vera.Eur J Haematol. 1997 Nov;59(5):310-7. doi: 10.1111/j.1600-0609.1997.tb01692.x.
• [25] Safety and efficacy of combination therapy of interferon-2 and ruxolitinib in polycythemia vera and myelofibrosis.Cancer Med. 2018 Aug;7(8):3571-3581. doi: 10.1002/cam4.1619. Epub 2018 Jun 22.
• [26] Anti-inflammatory cytokines hepatocyte growth factor and interleukin-11 are over-expressed in Polycythemia vera and contribute to the growth of clonal erythroblasts independently of JAK2V617F.Oncogene. 2011 Feb 24;30(8):990-1001. doi: 10.1038/onc.2010.479. Epub 2010 Nov 1.
• [27] Genetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms.Nat Commun. 2015 Apr 7;6:6691. doi: 10.1038/ncomms7691.
• [28] Defective expression of the SHP-1 phosphatase in polycythemia vera.Exp Hematol. 1999 Jul;27(7):1124-32. doi: 10.1016/s0301-472x(99)00043-0.
• [29] Genetic predisposition to molecular response in patients with myeloproliferative neoplasms treated with hydroxycarbamide.Leuk Res. 2013 Aug;37(8):917-21. doi: 10.1016/j.leukres.2013.03.013. Epub 2013 Apr 15.
• [30] Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients.Blood. 2016 Jan 21;127(3):333-42. doi: 10.1182/blood-2015-07-661983. Epub 2015 Oct 8.
• [31] The TLR3/TICAM-1 pathway is mandatory for innate immune responses to poliovirus infection.J Immunol. 2011 Nov 15;187(10):5320-7. doi: 10.4049/jimmunol.1101503. Epub 2011 Oct 12.
• [32] JAK-mutant myeloproliferative neoplasms.Curr Top Microbiol Immunol. 2012;355:119-33. doi: 10.1007/82_2011_170.
• [33] Polycythemia vera and essential thrombocythemia: 2017 update on diagnosis, risk-stratification, and management.Am J Hematol. 2017 Jan;92(1):94-108. doi: 10.1002/ajh.24607.
• [34] Lipocalin-2 is associated with modulation of disease phenotype in a patient with concurrent JAK2-V617F and BCR-ABL mutation.Eur J Haematol. 2012 Feb;88(2):175-8. doi: 10.1111/j.1600-0609.2011.01712.x. Epub 2011 Nov 17.
• [35] Fluorescence in situ hybridization analysis of 25 cases of idiopathic myelofibrosis and two cases of secondary myelofibrosis: monoallelic loss of RB1, D13S319 and D13S25 loci associated with cytogenetic deletion and translocation involving 13q14.Br J Haematol. 2001 May;113(2):365-8. doi: 10.1046/j.1365-2141.2001.02754.x.
• [36] Hb Kanagawa [alpha 40(C5)Lys----Met]: a new alpha chain variant with an increased oxygen affinity.Hemoglobin. 1992;16(1-2):1-10. doi: 10.3109/03630269209005670.
• [37] The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera.Haematologica. 2009 Nov;94(11):1537-45. doi: 10.3324/haematol.2009.007047. Epub 2009 Jul 16.
• [38] Whole blood transcriptional profiling reveals deregulation of oxidative and antioxidative defence genes in myelofibrosis and related neoplasms. Potential implications of downregulation of Nrf2 for genomic instability and disease progression.PLoS One. 2014 Nov 14;9(11):e112786. doi: 10.1371/journal.pone.0112786. eCollection 2014.
• [39] A conditional inducible JAK2V617F transgenic mouse model reveals myeloproliferative disease that is reversible upon switching off transgene expression.PLoS One. 2019 Oct 10;14(10):e0221635. doi: 10.1371/journal.pone.0221635. eCollection 2019.
• [40] A novel splicing site IRP1 somatic mutation in a patient with pheochromocytoma and JAK2(V617F) positive polycythemia vera: a case report.BMC Cancer. 2018 Mar 13;18(1):286. doi: 10.1186/s12885-018-4127-x.
• [41] t(5;12)(q23-31;p13) with ETV6-ACSL6 gene fusion in polycythemia vera.Leukemia. 2006 Jun;20(6):1175-8. doi: 10.1038/sj.leu.2404194.
• [42] An unconventional antigen translated by a novel internal ribosome entry site elicits antitumor humoral immune reactions.J Immunol. 2006 Oct 1;177(7):4907-16. doi: 10.4049/jimmunol.177.7.4907.
• [43] Phosphoproteomic Landscaping Identifies Non-canonical cKIT Signaling in Polycythemia Vera Erythroid Progenitors.Front Oncol. 2019 Nov 22;9:1245. doi: 10.3389/fonc.2019.01245. eCollection 2019.
• [44] MLF1IP promotes normal erythroid proliferation and is involved in the pathogenesis of polycythemia vera.FEBS Lett. 2017 Mar;591(5):760-773. doi: 10.1002/1873-3468.12587. Epub 2017 Feb 24.
• [45] Cholesterol 25-hydroxylase acts as a host restriction factor on pseudorabies virus replication.J Gen Virol. 2017 Jun;98(6):1467-1476. doi: 10.1099/jgv.0.000797. Epub 2017 Jun 20.
• [46] der(1)t(1;9): a specific chromosome abnormality in polycythemia vera? Cytogenetic and in situ hybridization studies.Cancer Genet Cytogenet. 1989 Jul 1;40(1):121-7. doi: 10.1016/0165-4608(89)90153-2.
• [47] Novel tumor antigens elicit anti-tumor humoral immune reactions in a subset of patients with polycythemia vera.Clin Immunol. 2007 Mar;122(3):279-87. doi: 10.1016/j.clim.2006.10.006. Epub 2006 Nov 17.
• [48] Dysregulated iron metabolism in polycythemia vera: etiology and consequences.Leukemia. 2018 Oct;32(10):2105-2116. doi: 10.1038/s41375-018-0207-9. Epub 2018 Jul 24.
• [49] Cytogenetic studies on acute nonlymphocytic leukemias following polycythemia vera.Cancer Genet Cytogenet. 1984 Apr;11(4):441-51. doi: 10.1016/0165-4608(84)90025-6.
• [50] Case of polycythemia vera concurrent with FIP1L1-PDGFRA-positive myeloproliferative neoplasm with eosinophilia.Cancer Genet. 2012 Oct;205(10):519-22. doi: 10.1016/j.cancergen.2012.05.010. Epub 2012 Sep 1.
• [51] Methylome profiling reveals distinct alterations in phenotypic and mutational subgroups of myeloproliferative neoplasms.Cancer Res. 2013 Feb 1;73(3):1076-85. doi: 10.1158/0008-5472.CAN-12-0735. Epub 2012 Oct 11.
• [52] Structural, antigenetic and transcriptional characteristics in peripheral blood CD34+ progenitor cells from polycythemia vera patients: evidence for delayed determination.Int J Oncol. 2003 Aug;23(2):437-43.
• [53] Alphaherpesvirus infection of mice primes PNS neurons to an inflammatory state regulated by TLR2 and type I IFN signaling.PLoS Pathog. 2019 Nov 1;15(11):e1008087. doi: 10.1371/journal.ppat.1008087. eCollection 2019 Nov.
• [54] Selection of cellular genetic markers for the detection of infectious poliovirus.J Appl Microbiol. 2018 Apr;124(4):1001-1007. doi: 10.1111/jam.13621. Epub 2018 Jan 11.
• [55] Aberrant expression of microRNA in polycythemia vera.Haematologica. 2008 Jul;93(7):1009-16. doi: 10.3324/haematol.12706. Epub 2008 May 27.
• [56] Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2.Blood. 2005 Nov 15;106(10):3374-6. doi: 10.1182/blood-2005-05-1889. Epub 2005 Aug 4.
• [57] Depletion of L3MBTL1 promotes the erythroid differentiation of human hematopoietic progenitor cells: possible role in 20q- polycythemia vera.Blood. 2010 Oct 14;116(15):2812-21. doi: 10.1182/blood-2010-02-270611. Epub 2010 Jun 28.
• [58] Increased adhesion to endothelial cells of erythrocytes from patients with polycythemia vera is mediated by laminin alpha5 chain and Lu/BCAM.Blood. 2007 Aug 1;110(3):894-901. doi: 10.1182/blood-2006-10-048298. Epub 2007 Apr 5.
• [59] Transcriptional alteration of DNA repair genes in Philadelphia chromosome negative myeloproliferative neoplasms.Ann Hematol. 2019 Dec;98(12):2703-2709. doi: 10.1007/s00277-019-03836-2. Epub 2019 Nov 20.
• [60] The presence of monoclonal gammopathy in Ph-negative myeloproliferative neoplasms is associated with a detrimental effect on outcomes.Leuk Lymphoma. 2017 Nov;58(11):2582-2587. doi: 10.1080/10428194.2017.1312380. Epub 2017 May 9.
• [61] Fusion protein consisting of the first immunoglobulin-like domain of porcine nectin-1 and Fc portion of human IgG1 provides a marked resistance against pseudorabies virus infection to transgenic mice.Microbiol Immunol. 2009 Jan;53(1):8-15. doi: 10.1111/j.1348-0421.2008.00082.x.
• [62] Transcriptional profiling of polycythemia vera identifies gene expression patterns both dependent and independent from the action of JAK2V617F.Clin Cancer Res. 2010 Sep 1;16(17):4339-52. doi: 10.1158/1078-0432.CCR-10-1092. Epub 2010 Jul 2.
• [63] PTP-MEG2 is activated in polycythemia vera erythroid progenitor cells and is required for growth and expansion of erythroid cells.Blood. 2003 Dec 15;102(13):4354-60. doi: 10.1182/blood-2003-04-1308. Epub 2003 Aug 14.
• [64] Poliomyelitis in transgenic mice expressing CD155 under the control of the Tage4 promoter after oral and parenteral poliovirus inoculation.J Gen Virol. 2014 Aug;95(Pt 8):1668-1676. doi: 10.1099/vir.0.064535-0. Epub 2014 Apr 30.
• [65] Sprouty proteins are negative regulators of interferon (IFN) signaling and IFN-inducible biological responses.J Biol Chem. 2012 Dec 7;287(50):42352-60. doi: 10.1074/jbc.M112.400721. Epub 2012 Oct 16.
• [66] pSTAT5 and ERK exhibit different expression in myeloproliferative neoplasms.Oncol Rep. 2017 Apr;37(4):2295-2307. doi: 10.3892/or.2017.5476. Epub 2017 Feb 24.
• [67] Essential role for Stat5a/b in myeloproliferative neoplasms induced by BCR-ABL1 and JAK2(V617F) in mice.Blood. 2012 Apr 12;119(15):3550-60. doi: 10.1182/blood-2011-12-397554. Epub 2012 Jan 10.