DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for essential thrombocythemia — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEssential thrombocythemia maps to a 44-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for essential thrombocythemia is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
isocitrate dehydrogenase (NADP(+)) 2 (IDH2) — IDH2 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5I96 · 1.55 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 605 patients with essential thrombocythemia followed for 4596 person-years, the 10-year risk of thrombosis was 14%, with age over 60 and a history of thrombosis as independent risk factors. Progression to myelofibrosis occurred in 2.8% of patients (10-year risk 3.9%), and leukaemia in 2.3% (10-year risk 2.6%), with a median time to leukaemia of 11 years. Cytotoxic treatment did not imply a higher risk of leukaemia. The 10-year probability of survival was 88%, with a median survival of 22.3 years. The same 2008 study notes that drug therapy in essential thrombocythemia has not been shown to positively influence the risk of leukaemic or fibrotic transformation, though a controlled study demonstrated the antithrombotic value of hydroxyurea in high-risk patients.
Molecular lesions in essential thrombocythemia affect cytokine signalling and transcriptional regulation pathways. Signalling pathway mutations drive myeloproliferation, while the phenotypic consequences of transcriptional pathway mutations remain unclear. Clonal heterogeneity has been revealed, but its clinical significance is not yet understood. In children, essential thrombocythemia is roughly 100-fold rarer than in adults, and clonal markers are found in only 25.8% of paediatric cases compared with 80–90% in adults. A 2015 study investigated JAK2 V617F, MPL, and CALR mutations in a large cohort of children with ET and performed targeted next-generation sequencing, but no additional mutations had been reported in childhood ET at that time.
Anagrelide, reviewed in 1999, induces thrombocytopenia in thrombocythemic patients with a reduction in disease-related symptoms and is described as lacking leukemogenic or mutagenic potential. The review states that the treatment of choice for thrombocythemia remains an area of debate, but that anagrelide has distinct advantages over alternative therapies.
What is still missing is a complete genetic lexicon for essential thrombocythemia, particularly in children, where clonal markers are scarce and molecular distinction from reactive thrombocytosis remains difficult. The clinical significance of clonal heterogeneity in adults is unclear, and no drug therapy has been shown to reduce the risk of leukaemic or fibrotic transformation. Prospective trials that stratify patients by molecular subtype and adequately track long-term outcomes, especially in paediatric populations, are lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Haematologica · 2008 · 262 citations · open access
Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients
AbstractBACKGROUND: Essential thrombocythemia is a chronic myeloproliferative disorder; patients with this disorder have a propensity to develop thrombosis, myelofibrosis, and leukemia. DESIGN AND METHODS: We studied 605 patients with essential thrombocythemia (follow-up 4596 person-years) with the aim of defining prognostic factors for thrombosis, myelofibrosis, and leukemia during follow-up. RESULTS: Sixty-six patients (11%) developed thrombosis with a 10-year risk of 14%. Age >60 years (p<0.001) and a history of thrombosis (p=0.03) were independent risk factors for thrombosis. Progression to myelofibrosis occurred in 17 patients (2.8%) with a 10-year risk of 3.9%. Anemia at diagnosis of essential thrombocythemia was significantly correlated (p<0.001) with progression to myelofibrosis. Leukemia occurred in 14 patients (2.3%) at a median time of 11 years after the diagnosis of essential thrombocythemia; the risk was 2.6% at 10 years. Age >60 years (p=0.02) was significantly correlated with the development of leukemia. Cytotoxic treatment did not imply a higher risk of leukemia. At the time of the analysis, 64 of the 605 patients (10.6%) had died. The 10-year probability of survival was 88%, with a median survival of 22.3 years. Age >60 years (p<0.001) and history of thrombosis (p=0.001) were independent risk factors for survival. CONCLUSIONS: The findings from this study on a large series of patients treated according to current clinical practice provide reassurance that essential thrombocythemia is an indolent disorder and affected patients have a long survival. The main risk is thrombosis, while myelofibrosis and leukemia are rare and late complications.
Distinct molecular abnormalities underlie unique clinical features of essential thrombocythemia in children
AbstractEssential thrombocythemia (ET) is rare in children, with an annual incidence of ~100-fold lower than that in adults. 1 The rarity of the disease in children makes the clinical course and pathogenesis of childhood ET far less clear. It is reported that clonal markers are much less common in children with ET (25.8%) than that in adult cases (80–90%). 2 , 3 , 4 Except for JAK2 V617F, and MPL and calreticulin ( CALR ) mutations, no other mutations have yet been reported in childhood ET. 2 , 5 , 6 , 7 , 8 More molecular markers are needed to distinguish clonal from reactive thrombocytosis in children. The present study investigated the JAK2 V617F, and MPL and CALR mutations in a large cohort of children with ET. We conducted the first study to analyze the molecular profiles by targeted next-generation sequencing and to investigate the JAK2 46/1 haplotype in childhood ET.
Current Opinion in Hematology · 2011 · 17 citations
The pathogenesis of essential thrombocythemia
AbstractPURPOSE OF REVIEW: The identification of new mutations continues to further our understanding of the molecular pathogenesis of essential thrombocythemia and related disorders, and offers opportunities for improvements in diagnosis, risk stratification and disease classification. RECENT FINDINGS: Molecular lesions in essential thrombocythemia affect two distinct pathways: cytokine signaling and transcriptional regulation. Signaling pathway mutations show a high degree of phenotypic specificity, in contrast to alterations in transcriptional pathways in which the same mutations are seen in diverse myeloid malignancies. Signaling pathway mutations are directly implicated in driving the myeloproliferation which characterizes essential thrombocythemia, whereas the phenotypic consequences of transcriptional pathway mutations are yet to be elucidated. The expanding lexicon of genetic abnormalities has revealed a surprising degree of clonal heterogeneity in essential thrombocythemia, although the clinical significance of this clonal complexity is currently unclear. Potential clinical applications for mutation screening include streamlining of the diagnostic process, improved risk stratification, and molecular distinction of essential thrombocythemia from related disorders such as polycythemia vera and myelofibrosis. SUMMARY: The genetic lexicon of essential thrombocythemia remains incomplete. Given the current acceleration in sequencing technology, further insights into essential thrombocythemia pathogenesis are likely close at hand.
Platelet count in essential thrombocythemia: the more the better?
AbstractTo the editor:
To date, drug therapy in essential thrombocythemia (ET) has not been shown to positively influence the risk of leukemic or fibrotic transformation. In contrast, an often-cited controlled study[1][1] has demonstrated the antithrombotic value of hydroxyurea therapy in high-risk
Role of Anagrelide in the Treatment of Thrombocytosis
AbstractOBJECTIVE: To review the role of anagrelide in the management of essential thrombocythemia. DATA SOURCES: A MEDLINE search (January 1966-August 1998) was performed using the key terms anagrelide, thrombocytosis, and essential thrombocythemia. In addition, the package insert, product monograph, and patient information pamphlets were reviewed. DATA SYNTHESIS: Recently, there has been a trend toward the use of anagrelide in the management of thrombocythemia. Anagrelide lacks leukemogenic and mutagenic potential and possesses a more favorable adverse effect profile compared with other therapeutic agents. At recommended doses, anagrelide induces thrombocytopenia in thrombocythemic patients with a concomitant reduction in the incidence of disease-related symptoms. CONCLUSIONS: Although the treatment of choice for thrombocythemia is still an area of debate, anagrelide has distinct advantages over alternative therapies. Anagrelide represents an important therapeutic option in the treatment of patients with thrombocythemia.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
