Myelofibrosis

Disease ID:655
Name:Myelofibrosis
Associated with:3 targets
1 immuno-relevant target
2 immuno-relevant ligands
Synonyms
Myelofibrosis with myeloid metaplasia
Database Links
Disease Ontology: DOID:4971
OMIM: 254450
Orphanet: ORPHA824

Targets

NK1 receptor
References:  2,5-6
Thrombopoietin receptor
Janus kinase 2
Comments:  Somatic mutations in the JAK2 gene have been identified in many cases of myelofibrosis.
Ligand interactions: 
Ligand Comments
ruxolitinib
Approved drug for myelofibrosis, in particular for primary myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocyt ...
itacitinib
Phase 2 clinical candidate for myelofibrosis (see NCT03144687).

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
ruxolitinib
Immuno Disease Comments: Approved drug for myelofibrosis, in particular for primary myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocythemia (post-ET) myelofibrosis.
Clinical Use: Used to treat intermediate or high-risk myelofibrosis including including primary myelofibrosis, post-polycythemia vera (post-PV) myelofibrosis and post-essential thrombocythemia (post-ET) myelofibrosis.
In 2014 ruxolitinib was approved for the new use of treating patients with polycythemia vera, a chronic type of bone marrow disease.

Interesting results from small trials in patients with alopecia areata suggest that by killing the immune cells responsible for hair loss in this disease, ruxolitinib can promote hair re-growth [4,7]. | View clinical data
itacitinib
Immuno Disease Comments: Phase 2 clinical candidate for myelofibrosis (see NCT03144687).
Clinical Use: INCB039110 is being assessed in Phase II clinical trial as a potential treatment for indications such as rheumatoid arthritis (RA), post essential thrombocythemia myelofibrosis, chronic plaque psoriasis and non-small cell lung cancer (NSCLC). | View clinical data

References

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1. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N et al.. (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet, 365 (9464): 1054-61. [PMID:15781101]

2. Chang VT, Yook C, Rameshwar P. (2013) Synergism between fibronectin and transforming growth factor-β1 in the production of substance P in monocytes of patients with myelofibrosis. Leuk. Lymphoma, 54 (3): 631-8. [PMID:22906243]

3. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC. (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N. Engl. J. Med., 352 (17): 1779-90. [PMID:15858187]

4. Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, Furniss M, Vaughan R, Christiano AM, R Clynes R. (2016) Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight, 1 (15): e89790 Epub.

5. Rameshwar P, Joshi DD, Yadav P, Qian J, Gascon P, Chang VT, Anjaria D, Harrison JS, Song X. (2001) Mimicry between neurokinin-1 and fibronectin may explain the transport and stability of increased substance P immunoreactivity in patients with bone marrow fibrosis. Blood, 97 (10): 3025-31. [PMID:11342427]

6. Rameshwar P, Oh HS, Yook C, Gascon P, Chang VT. (2003) Substance p-fibronectin-cytokine interactions in myeloproliferative disorders with bone marrow fibrosis. Acta Haematol., 109 (1): 1-10. [PMID:12486316]

7. Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, Rothman L et al.. (2014) Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat. Med., 20 (9): 1043-9. [PMID:25129481]