DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for acute megakaryoblastic leukaemia — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAcute megakaryoblastic leukaemia maps to a 7-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 acute megakaryoblastic leukaemia 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
phosphatase and tensin homolog (PTEN) — PTEN 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…
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RCSB Protein Data Bank · entry 1D5R · 2.1 Å · ligand L(+)-TARTARIC ACID (TLA). Experimental structure, not a prediction.
What the evidence adds up to
In a multicentre study of 57 patients with acute megakaryoblastic leukaemia (M7-AML), median age 49 years, median follow-up was 7 months. Among 45 patients treated with either combined aggressive chemotherapy (n=26) or low-dose cytarabine (n=19), complete remission rates were 73% and 84% respectively, 12-month survival 37% and 26%, 24-month survival 12% and 11%, median survival 10 and 4 months, and relapse rates 68% and 94%. None of these differences were statistically significant. Children (n=10) fared better than adults (n=35) on several measures — median survival 7 versus 5 months, 12-month survival 40% versus 22%, 24-month survival 30% versus 9% — but again the differences were not statistically significant. Relapse rates were 78% in children and 81% in adults. A literature review of 42 additional patients included seven treated with allogeneic bone marrow transplantation, for whom 12- and 24-month survival was 86% and relapse rate 0%.
A 2021 case report describes a patient with acute myeloid leukaemia with myelodysplasia-related changes and megakaryoblastic differentiation, notable for CD34 positivity in abnormal megakaryoblasts and absence of recurrent genomic lesions such as t(1;22), inv(3) or t(3;3). Another 2021 study of young children with AMKL reports a case with 52% blast cells expressing megakaryocyte markers cCD41, CD61 and CD36, a complex karyotype including der(3) and del(13), and overexpression of WT1 together with positivity for MLL-PTD and EVI1. Peroxidase, AS-DNCE and alpha-NBE stains were negative.
The 1992 study is small, retrospective, and spans a wide age range with short follow-up. No treatment regimen produced durable remissions in adults; low-dose cytarabine yielded high initial remission but near-universal relapse. Bone marrow transplantation data come from a literature review of only seven patients, not a controlled trial. The more recent reports are single cases or small series describing immunophenotypic and genetic complexity but provide no treatment outcomes. What is still missing is a prospective trial large enough to stratify patients by age, cytogenetics, and molecular markers, and to test whether targeted agents or transplantation can improve the uniformly poor long-term survival seen in the only multicentre study available.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Haematology · 1992 · 25 citations
Long‐term treatment results for acute megakaryoblastic leukaemia patients: a multicentre study
AbstractThe prognosis and long-term results of a group of 57 acute megakaryoblastic leukaemia (M7-AML) patients was analysed from a multicentre perspective. Ages ranged from 4 to 83 years, median 49 years; 30 were males and 27 were females. The median follow-up time was 7 months, range 1-24 months. Early exits occurred in 12 cases, their median age being 71 years. Forty-five patients were treated with combined aggressive chemotherapy (CT) (n = 26) or low-dose cytarabine (LD-AraC) (n = 19). The following results were obtained with combined CT or AraC, respectively. Complete remission (CR) rates were 73% and 84%, 12-month survival (SV) were 37% and 26%, 24-month SV were 12% and 11%, median SV 10 and 4 months, and relapse rates (RR) were 68% and 94%. These differences were not statistically significant. Irrespective of the treatment modality, the results were better for children (n = 10) than for adults (n = 35): RR rates were 90% and 74%, median SV: 7 and 5 months, 12-month SV: 40% and 22%, 24-month SV; 30% and 9%, and RR: 78% and 81%, respectively; these differences also were not statistically significant. In addition, a literature review of 42 patients from 18 previous reports is presented, including seven cases treated with allogeneic bone marrow transplantation (BMT). The best results were obtained with BMT: 12 and 24 month SV was 86% and the RR was 0%. On the above-mentioned basis, we feel that children and young adults with M7-AML should be offered BMT. In patients over 60 years old or not eligible for aggressive chemotherapy or BMT, an interesting possibility would be the use of LD-AraC which allows a high CR rate, followed by a classical consolidation regimen in order to prevent early relapses.
Unusual CD34 positivity in acute myeloid leukaemia with myelodysplasia‐related changes with megakaryoblastic differentiation
AbstractAcute megakaryoblastic leukaemia is a rare entity with distinct immunophenotype profile and cytogenetic lesions. Herein, we report a case of acute myeloid leukaemia with myelodysplastic-related changes with megakaryoblastic differentiation in absence of recurrent genomic lesions such as t(1;22), inv(3) and t(3;3). One of the peculiarities of this case is the positivity of CD34+ within the abnormal megakaryoblasts; CD61 immunohistochemistry highlights the heavily infiltration of bone marrow from abnormal megakaryoblasts.
[Phenotypic and genetic analysis of acute megakaryoblastic leukemia in young children with WT1, MLL-PTD and EVI1 genes].
AbstractOBJECTIVE: To explore the phenotypic and genetic characteristics of acute megakaryoblastic leukemia (AMKL) in young children accompany by WT1, MLL-PTD and EVI1, in order to improve the diagnosis level of AMKL. METHODS: anticoagulation venous blood was collected for blood routine and morphological analysis of blood cells; bone marrow was extracted for cell morphology, immunophenotype, chromosome karyotype and fusion gene analysis. RESULTS: /L. The morphological analysis of blood cells showed that the size of immature cells was like that of primitive immature lymphocytes, which was circular or irregular and part of them with obvious pseudopodia. The cytoplasm is basophilic with heterogeneous coloration and granules. Nuclear chromatin is fine and even, 1-3 nucleoli can be seen, these immature cells account for about 40%; the morphology of bone marrow cells was consistent with acute leukemia, negative for peroxidase staining, negative for AS-DNCE staining and alpha-NBE staining. Flow cytometry results showed that the protocells account for about 52% and significant expression of megakaryocytes related markers (cCD41+, CD61+, CD36+). Chromosome karyotype is 46, XX, der(3) add(3)(p21)add(3)(q25), add (9)(q22), -13, +mar [4]/46, XX, del(13)(q12q22) [3]/46, XX[3]. The fusion gene WT1 was overexpressed, MLL-PTD and EVI1 were positive. CONCLUSION: Acute megakaryocytic leukemia has unique and complex phenotypic and genetics characteristics.
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.
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