Details of Disease

General Information of Disease (ID: DISIMP21)

• Disease Name: Myelofibrosis
• Synonyms: myelofibrosis
• Disease Class: 2A20: Myeloproliferative neoplasm
• Definition: A partial or complete replacement of the bone marrow stroma by fibrous tissue. It can be a primary bone marrow lesion as part of the chronic myeloproliferative disorders (chronic idiopathic myelofibrosis), a manifestation of acute myeloid leukemia (acute panmyelosis with myelofibrosis), or a secondary phenomenon due to bone marrow involvement by a metastatic tumor (e.g., metastatic breast carcinoma). --2003
• Disease Hierarchy:
  DIS5KAPA: Myeloproliferative neoplasm
  DISIMP21: Myelofibrosis
• ICD Code:
  ICD-11: ICD-11: 2A20.2
  ICD-10: ICD-10: D47.4
  Expand ICD-11: '2A20.2
  Expand ICD-10: 'D47.4
  Expand ICD-9: 208.9,289.83,709.2
• Disease Identifiers:
  MONDO ID: MONDO_0044903
  UMLS CUI: C0026987
  OMIM ID: 254450
  MedGen ID: 10146
  HPO ID: HP:0011974
  SNOMED CT ID: 52967002

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 5 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]
Pacritinib	DM1T6ZN	Approved	Small molecular drug	[3]
Ruxolitinib	DM7Q98D	Approved	Small molecular drug	[4]
Teriparatide	DMMC45B	Approved	Peptide	[5]

This Disease is Treated as An Indication in 15 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
ABT-263	DMNE56X	Phase 3	Small molecular drug	[6]
ACE-536	DMRI15Q	Phase 3	NA	[7]
CPI-0610	DMPXOYJ	Phase 3	NA	[8]
ITF2357	DMFZBNE	Phase 3	Small molecular drug	[9]
P-1101	DM7WYXJ	Phase 3	NA	[10]
Pracinostat	DMTD7AB	Phase 3	Small molecular drug	[11]
Imetelstat	DMONWJ4	Phase 2/3	Small molecular drug	[10]
9-ING-41	DM57TY3	Phase 2	Small molecular drug	[12]
BMS-911543	DMF46PD	Phase 2	Small molecular drug	[13]
IMG-7289	DML9AVG	Phase 2	NA	[7]
LCL161	DMTM4QA	Phase 2	NA	[7]
PRM-151	DMK8PTH	Phase 2	NA	[10]
NS-018	DMU9BCD	Phase 1/2	Small molecular drug	[14]
PIM447	DMU26OE	Phase 1	NA	[7]
PU-H71	DMIYHAW	Phase 1	Small molecular drug	[7]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 9 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ABL1	TT6B75U	moderate	Biomarker	[15]
FLT3	TTGJCWZ	moderate	Biomarker	[16]
IRAK1	TTXAJWN	moderate	Altered Expression	[17]
SCT	TTOBVIN	moderate	Biomarker	[18]
CD34	TTZAVYN	Strong	Biomarker	[19]
HMGA2	TTSTVM0	Strong	Altered Expression	[20]
MVD	TTE5J6X	Strong	Biomarker	[21]
MYB	TT8V13P	Strong	Biomarker	[22]
SLCO2A1	TTKVTQO	Strong	Biomarker	[23]

This Disease Is Related to 27 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
BORA	OTV2ZPKP	Limited	Altered Expression	[24]
FGF3	OT9PK2SI	Limited	Biomarker	[25]
GATA1	OTX1R7O1	Limited	Genetic Variation	[26]
INTS2	OT2N5TCK	Limited	Biomarker	[25]
NCOR2	OTY917X0	Limited	Biomarker	[27]
TET2	OTKKT03T	Limited	Genetic Variation	[28]
BCR	OTCN76C1	moderate	Biomarker	[29]
DERL1	OTJUS74N	moderate	Genetic Variation	[30]
FXYD5	OT81DIOD	moderate	Biomarker	[31]
MPIG6B	OTVNKQWA	moderate	Genetic Variation	[32]
NBEAL2	OTMCAXWR	moderate	Genetic Variation	[33]
NOG	OTGRHHPG	moderate	Biomarker	[34]
BMF	OT90NSLI	Strong	Genetic Variation	[35]
CD177	OTS79FNF	Strong	Genetic Variation	[36]
EDA	OTAKS5WS	Strong	Biomarker	[37]
FZD2	OT952ML1	Strong	Altered Expression	[20]
GFI1B	OTRDW8YO	Strong	Altered Expression	[38]
INTS1	OT7TY1M1	Strong	Biomarker	[25]
LIG3	OT48SKET	Strong	Altered Expression	[39]
MYOM2	OTD2UOXW	Strong	Biomarker	[40]
NFE2	OTLM94BI	Strong	Biomarker	[41]
PRB1	OTV0SYMD	Strong	Genetic Variation	[24]
PRSS27	OTC4G4UF	Strong	Biomarker	[42]
RARS1	OTHPZ6JN	Strong	Biomarker	[43]
RPS14	OTB90KV5	Strong	Biomarker	[44]
SHOC2	OTUNQ2CT	Strong	Genetic Variation	[45]
SOAT1	OTB4Y5RJ	Definitive	Biomarker	[46]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 216873
• [3] FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 208712.
• [4] Ruxolitinib FDA Label
• [5] Teriparatide FDA Label
• [6] ClinicalTrials.gov (NCT04472598) Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis (TRANSFORM-1). U.S. National Institutes of Health.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] ClinicalTrials.gov (NCT04603495) Study of CPI-0610 in Myelofibrosis (MF) (MANIFEST-2). U.S. National Institutes of Health.
• [9] 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).
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] 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: 8365).
• [12] ClinicalTrials.gov (NCT04218071) Actuate 1901: 9-ING-41 in Myelofibrosis. U.S. National Institutes of Health.
• [13] 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: 7954).
• [14] 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: 7839).
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• [18] Bone marrow mesenchymal stromal cells remain of recipient origin after allogeneic SCT and do not harbor the JAK2V617F mutation in patients with myelofibrosis.Clin Exp Med. 2010 Sep;10(3):205-8. doi: 10.1007/s10238-009-0058-9. Epub 2009 Jul 23.
• [19] A thrombopoietin receptor antagonist is capable of depleting myelofibrosis hematopoietic stem and progenitor cells.Blood. 2016 Jun 30;127(26):3398-409. doi: 10.1182/blood-2015-10-674465. Epub 2016 Apr 25.
• [20] Hmga2 promotes the development of myelofibrosis in Jak2(V617F) knockin mice by enhancing TGF-1 and Cxcl12 pathways.Blood. 2017 Aug 17;130(7):920-932. doi: 10.1182/blood-2016-12-757344. Epub 2017 Jun 21.
• [21] MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis.Blood. 2014 Aug 14;124(7):1183-91. doi: 10.1182/blood-2014-04-572545. Epub 2014 Jun 24.
• [22] A recessive screen for genes regulating hematopoietic stem cells.Blood. 2010 Dec 23;116(26):5849-58. doi: 10.1182/blood-2010-04-269951. Epub 2010 Jul 7.
• [23] Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis.Hum Mutat. 2012 Aug;33(8):1175-81. doi: 10.1002/humu.22111. Epub 2012 May 29.
• [24] Higher AURKA and PLK1 expression are associated with inferior overall survival in patients with myelofibrosis.Blood Cells Mol Dis. 2020 Mar;81:102396. doi: 10.1016/j.bcmd.2019.102396. Epub 2019 Dec 5.
• [25] Genetically inspired prognostic scoring system (GIPSS) outperforms dynamic international prognostic scoring system (DIPSS) in myelofibrosis patients.Am J Hematol. 2019 Jan;94(1):87-92. doi: 10.1002/ajh.25335. Epub 2018 Nov 25.
• [26] Highly sensitive detection of GATA1 mutations in patients with myeloid leukemia associated with Down syndrome by combining Sanger and targeted next generation sequencing.Genes Chromosomes Cancer. 2020 Mar;59(3):160-167. doi: 10.1002/gcc.22816. Epub 2019 Oct 21.
• [27] Rescue of a primary myelofibrosis model by retinoid-antagonist therapy.Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18820-5. doi: 10.1073/pnas.1318974110. Epub 2013 Nov 4.
• [28] Next-generation sequencing with a 54-gene panel identified unique mutational profile and prognostic markers in Chinese patients with myelofibrosis.Ann Hematol. 2019 Apr;98(4):869-879. doi: 10.1007/s00277-018-3563-7. Epub 2018 Dec 4.
• [29] Understanding Splenomegaly in Myelofibrosis: Association with Molecular Pathogenesis.Int J Mol Sci. 2018 Mar 18;19(3):898. doi: 10.3390/ijms19030898.
• [30] Translocation t(1;9) is a recurrent cytogenetic abnormality associated with progression of essential thrombocythemia patients displaying the JAK2 V617F mutation.Leuk Res. 2011 Sep;35(9):1188-92. doi: 10.1016/j.leukres.2011.02.001. Epub 2011 Mar 3.
• [31] Allogeneic hematopoietic stem cell transplantation with fludarabine, busulfan, and thiotepa conditioning is associated with favorable outcomes in myelofibrosis.Bone Marrow Transplant. 2020 Jan;55(1):147-156. doi: 10.1038/s41409-019-0653-7. Epub 2019 Aug 28.
• [32] Uncoupling ITIM receptor G6b-B from tyrosine phosphatases Shp1 and Shp2 disrupts murine platelet homeostasis.Blood. 2018 Sep 27;132(13):1413-1425. doi: 10.1182/blood-2017-10-802975. Epub 2018 Jun 11.
• [33] A Case of Chronic Thrombocytopenia in a 17-Year-Old Female.Lab Med. 2019 Oct 10;50(4):406-420. doi: 10.1093/labmed/lmz013.
• [34] Increased SLAMF7(high) monocytes in myelofibrosis patients harboring JAK2V617F provide a therapeutic target of elotuzumab.Blood. 2019 Sep 5;134(10):814-825. doi: 10.1182/blood.2019000051. Epub 2019 Jul 3.
• [35] Transforming growth factor - and interleukin 13-producing mast cells are associated with fibrosis in bone marrow.Hum Pathol. 2017 Apr;62:180-186. doi: 10.1016/j.humpath.2017.01.007. Epub 2017 Jan 31.
• [36] Deregulation of apoptosis-related genes is associated with PRV1 overexpression and JAK2 V617F allele burden in Essential Thrombocythemia and Myelofibrosis.J Hematol Oncol. 2012 Feb 2;5:2. doi: 10.1186/1756-8722-5-2.
• [37] EDA fibronectin-TLR4 axis sustains megakaryocyte expansion and inflammation in bone marrow fibrosis.J Exp Med. 2019 Mar 4;216(3):587-604. doi: 10.1084/jem.20181074. Epub 2019 Feb 7.
• [38] Growth factor-independent 1B gene (GFI1B) is overexpressed in erythropoietic and megakaryocytic malignancies and increases their proliferation rate.Br J Haematol. 2007 Jan;136(2):212-9. doi: 10.1111/j.1365-2141.2006.06407.x. Epub 2006 Dec 8.
• [39] 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.
• [40] 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.
• [41] A role of NF-E2 in chronic inflammation and clonal evolution in essential thrombocythemia, polycythemia vera and myelofibrosis?.Leuk Res. 2014 Feb;38(2):263-6. doi: 10.1016/j.leukres.2013.07.002. Epub 2013 Aug 9.
• [42] Improvement of the hematologic toxicities of ruxolitinib in patients with MPN-associated myelofibrosis using a combination of thalidomide, stanozolol and prednisone.Hematology. 2019 Dec;24(1):516-520. doi: 10.1080/16078454.2019.1631509.
• [43] The role of JAK2 mutations in RARS and other MDS.Hematology Am Soc Hematol Educ Program. 2008:52-9. doi: 10.1182/asheducation-2008.1.52.
• [44] The thrombopoietin/MPL axis is activated in the Gata1(low) mouse model of myelofibrosis and is associated with a defective RPS14 signature.Blood Cancer J. 2017 Jun 16;7(6):e572. doi: 10.1038/bcj.2017.51.
• [45] Expanding the SHOC2 mutation associated phenotype of Noonan syndrome with loose anagen hair: structural brain anomalies and myelofibrosis.Am J Med Genet A. 2013 Oct;161A(10):2420-30. doi: 10.1002/ajmg.a.36098. Epub 2013 Aug 5.
• [46] Cytokine production in myelofibrosis exhibits differential responsiveness to JAK-STAT, MAP kinase, and NFB signaling.Leukemia. 2019 Aug;33(8):1978-1995. doi: 10.1038/s41375-019-0379-y. Epub 2019 Feb 4.