DeCure for T-cell large granular lymphocyte leukemia
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for T-cell large granular lymphocyte leukemia — 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 moduleT-cell large granular lymphocyte leukemia 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 t-cell large granular lymphocyte leukemia 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
endothelial PAS domain protein 1 (EPAS1) — EPAS1 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 furan-2-ylmethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3H82 · 1.5 Å · ligand N-(furan-2-ylmethyl)-2-nitro-4-(trifluoromethyl)aniline (020). Experimental structure, not a prediction.
What the evidence adds up to
T-cell large granular lymphocyte leukemia is a chronic clonal lymphoproliferation of cytotoxic T cells often associated with immune-mediated cytopenias, particularly neutropenia and anaemia. The pathophysiology of these cytopenias includes cytokine effects and direct antigen-specific cytotoxicity to haematopoietic precursors. The disease may assume an indolent course but sometimes manifests with significant cytopenias, and a majority of patients will ultimately require immunosuppressive therapy. The neoplastic cells display a mature T-cell immunophenotype, with most cases showing a CD4−/CD8+ T-cell receptor subset.
Immunosuppressive therapy with cyclosporine, methotrexate, and oral cyclophosphamide is often used, but formal trials have not been performed and response rates are poorly established. In refractory cases, alternative regimens such as antithymocyte globulin or monoclonal antibody therapy have exhibited haematologic response, though chronic therapy is often necessary. A retrospective study of six patients treated with fludarabine at 40 mg/m² for three to five days per month for 6 to 8 cycles reported a complete haematologic response in all six cases and a complete molecular response in five out of six (83.3%). During a mean follow-up of 12 months, both progression-free survival and overall survival were 100%. Two patients received fludarabine as first-line treatment, two for refractory disease, one for relapsed disease after methotrexate was stopped due to liver toxicity, and one due to dyspepsia.
The fludarabine data come from a single retrospective study with only six patients, a median age of 36.5 years, and a short follow-up of 12 months. The authors themselves note that formal clinical trials are needed to confirm these results. The broader treatment landscape lacks randomised trials entirely, and response rates for standard immunosuppressants remain poorly established. What is still missing are prospective, adequately powered trials, longer follow-up to assess durability of responses, and clear stratification of patients by prior treatment lines, cytopenia severity, and molecular markers.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Hematology · 2008 · 53 citations
Diagnosis and therapy of neutropenia in large granular lymphocyte leukemia
AbstractPURPOSE OF REVIEW: T-cell large granular lymphocyte leukemia is a chronic clonal lymphoproliferation of cytotoxic T cells often associated with immune-mediated cytopenias. The pathophysiology of cytopenias includes cytokine effects and direct antigen-specific cytotoxicity to hematopoietic precursors. This review will address the diagnostic challenges of and therapeutic options for T-cell large granular lymphocyte leukemia. RECENT FINDINGS: Immunosuppressive therapy, with cyclosporine, methotrexate, and oral cyclophosphamide, is often used, but formal trials have not been performed and response rates are poorly established. In refractory cases, alternative regimens such as antithymocyte globulin or monoclonal antibody therapy have exhibited hematologic response. SUMMARY: T-cell large granular lymphocyte leukemia may assume an indolent course but sometimes manifests with significant cytopenias. A majority of patients will ultimately require immunosuppressive therapy due to symptomatic neutropenia or anemia. In these cases, a variety of agents maybe used successfully though chronic therapy is often necessary.
T-cell large granular lymphocytic leukemia: treatment experience with fludarabine
AbstractOBJECTIVES: The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival. METHODS: We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m², for three to five days per month and 6 to 8 cycles. RESULTS: Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4 x 10(9)/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment due to liver toxicity, and one (16.6%) due to dyspepsia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%. CONCLUSION: T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.
T-Cell Large Granular Lymphocytic Leukemia: A First Case Report Diagnosed by Flow Cytometry in Vietnam
AbstractT-cell large granular lymphocytic leukemia (T-LGL leukemia) is a rare, chronic lymphoproliferative disorder in the peripheral blood. This is characterized by peripheral blood and bone marrow (BM) lymphocytic infiltration with clonal large granular lymphocytes (LGLs). The neoplastic cells of this disease display a mature T-cell immunophenotype, with the majority of cases showing a CD4-/CD8+ T-cell, T-cell receptor (TCR) subset immunophenotype versus other permutations of those markers.
Anuario Jurídico y Económico Escurialense · 1998 · 0 citations · open access
Gonzálo Fernández de la Mora, crítico historiográfico
AbstractT-cell large granular lymphocytic leukemia (T-LGL leukemia) is a rare, chronic lymphoproliferative disorder in the peripheral blood. This is characterized by peripheral blood and bone marrow (BM) lymphocytic infiltration with clonal large granular lymphocytes (LGLs). The neoplastic cells of this disease display a mature T-cell immunophenotype, with the majority of cases showing a CD4-/CD8+ T-cell, T-cell receptor (TCR) subset immunophenotype versus other permutations of those markers.
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.
