DeCure for Minimally differentiated acute myeloblastic leukemia
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for minimally differentiated acute myeloblastic leukemia — screening already-approved drugs against its 30-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMinimally differentiated acute myeloblastic leukemia maps to a 30-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 minimally differentiated acute myeloblastic 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
ACD shelterin complex subunit and telomerase recruitment factor (ACD) — ACD 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 9SHY · 3.53 Å · ligand 2'-deoxy-5'-O-[(R)-hydroxy{[(S)-hydroxy(phosphonooxy)phosphoryl]methyl}phosphoryl]guanosine (1GC). Experimental structure, not a prediction.
What the evidence adds up to
The 1983 review notes that acute myelogenous leukaemia cells are blocked at an early stage and cannot differentiate into functional mature cells. It describes the development of human leukaemia cell lines as models for studying myeloid differentiation and for identifying chemical inducers of differentiation, but it does not report any clinical results in patients.
A 1992 review states that the traditional French-American-British morphological classification of acute myeloblastic leukaemia correlates poorly with cytogenetic, immunophenotypic and molecular data and does not predict response to therapy. A revised classification based on the presence or absence of myelodysplasia-like features is proposed, which the authors say correlates better with biologic data and therapeutic response. A 2022 article focuses on current laboratory diagnostics including morphology, histology, immunophenotyping and molecular parameters, but provides no treatment outcomes.
A 2011 retrospective study from Roswell Park examined 29 patients with acute leukaemias of ambiguous lineage, including mixed-phenotype acute leukaemia and acute undifferentiated leukaemia. Using the 2008 WHO criteria, only 6 of 29 cases (21%) were classified as acute leukaemias of ambiguous lineage, compared to 10 of 29 (34%) using the older EGIL system. Thirteen of the 29 cases (45%) met at least one set of criteria. The most common cytogenetic abnormality was t(9;22), found in 6 of 18 non-ambiguous cases (33%) and 2 of 13 ambiguous cases (15%). Patients classified as ambiguous lineage had a median overall survival of 12.25 months versus 20 months for non-ambiguous patients (p=0.08). Among ambiguous patients, those who received subsequent allogeneic stem cell transplantation after AML induction chemotherapy had the longest survivals (70.6, 27.1 and 17 months). Across all 29 patients, treatment with ALL-based chemotherapy was significantly associated with improved overall survival (p=0.015). The authors note that over half of the cases initially diagnosed as ambiguous were re-classified as ALL on review, and they support upfront treatment of acute leukaemia of unclear lineage with ALL-based regimens.
What is still missing is a prospective trial large enough to confirm whether ALL-based chemotherapy truly improves survival in these rare ambiguous-lineage leukaemias, and whether the benefit of allogeneic transplantation is limited to a specific subgroup. The retrospective data come from only 29 patients over 15 years at a single institution, so patient stratification by cytogenetic or molecular markers remains undefined.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 1983 · 579 citations · open access
Induction of differentiation of human acute myelogenous leukemia cells: therapeutic implications
AbstractA prominent phenotypic abnormality of human acute myelogenous leukemia cells is the inability of the cells to differentiate to functional mature cells; instead, the cells are blocked at an early stage of development and remain in the proliferative pool and rapidly accumulate. Investigation of the induction of myeloid leukemic cell differentiation has made recent advances with the development of several human myelogenous leukemia cell lines. The lines provide models to study the biology of myeloid differentiation and to identify inducers of differentiation of myeloid leukemic blood cells. This review critically examines the inducers of leukemic cell differentiation and their potential therapeutic importance.
Induction of differentiation of human acute myelogenous leukemia cells: therapeutic implications
AbstractA prominent phenotypic abnormality of human acute myelogenous leukemia cells is the inability of the cells to differentiate to functional mature cells; instead, the cells are blocked at an early stage of development and remain in the proliferative pool and rapidly accumulate. Investigation of the induction of myeloid leukemic cell differentiation has made recent advances with the development of several human myelogenous leukemia cell lines. The lines provide models to study the biology of myeloid differentiation and to identify inducers of differentiation of myeloid leukemic blood cells. This review critically examines the inducers of leukemic cell differentiation and their potential therapeutic importance.
AbstractIn recent years new developments in cytogenetics, immunophenotyping, and molecular biology have dramatically advanced our understanding of leukemia. Unfortunately, traditional morphologic evaluation of acute myeloblastic leukemia using the French-American-British classification correlates poorly with most of this new information and does not predict response to therapy. In this review we concentrate on applications of molecular biologic techniques to the diagnosis of leukemias, and discuss use of this technology to detect minimal residual disease. We then present a revised classification for acute myeloblastic leukemia according to whether myelodysplasia-like features are present or lacking. Cases may then be further classified using French-American-British morphology and other parameters. This classification appears to correlate better with new biologic data and with therapeutic response.
AbstractThe aim of the article is to approximate the possibilities of current laboratory diagnostics of acute myeloblastic leukemia (AML). AML diagnosis includes morphological, histological, immunofernotyping and molecular-biological parameters. We focus primarily on the morphological diagnostics of AML.
Acute Leukemias of Ambiguous Lineage: The Roswell Park Experience
AbstractAbstract Abstract 2546 Acute leukemias of ambiguous lineage (ALAL) are defined by the lack of clear evidence of differentiation along a single lineage and include mixed-phenotype acute leukemias (MPAL) and acute undifferentiated leukemia (AUL). These rare acute leukemias (AL) pose diagnostic and therapeutic challenges. Criteria for ALAL/MPAL diagnosis were proposed by the European Group for the Immunological Characterization of Leukemias (EGIL) and incorporated into the 2001 World Health Organization (WHO) classification of myeloid neoplasms. The most recent 2008 WHO classification proposed a much simplified diagnostic approach to MPAL/ALAL that requires clinical validation. We retrospectively analyzed the pathologic and clinical features of 29 cases of acute leukemia diagnosed and treated at our institution between 1995–2010. All AL patients with any of the following key words identified in the pathology and flow cytometry databases were reviewed: T/myeloid, B/myeloid, undifferentiated, mixed phenotype, anomalous expression, unclassified, biphenotypic, bilineal, biclonal. Pathology, flow cytometry, and cytogenetics reports were reviewed by 2 hematopathologists and reclassified according to EGIL and 2008 WHO criteria. Treatment regimens were reviewed and overall survival assessed for each patient. There were 29 patients,19 adults and 10 children, with a median age of 39 years (range 2–87). Eighteen were male and 11 female. Using EGIL, 10/29 (34%) were classified as ALAL as compared to 2008 WHO where only 6/29 (21%) fulfilled the new criteria. Based on either EGIL and/or 2008 WHO classification scheme,13 out of 29 cases (45%) were classified as ALAL. The remaining 16 cases were non-ALAL, most concordant in both systems: B-cell lymphoblastic leukemia (B-ALL) (n=11, 38%) and T ALL (n=3, 10%) and discrepant in only 2 cases (7%), both classified as acute myeloid leukemia (AML) by EGIL and B-ALL by 2008 WHO. The most common cytogenetic change was t(9;22), present in 6 (33%) of non-ALAL and 2/13 (15%) ALAL. A single 11q23 translocation case was seen in the non-ALAL group. We compared ALAL (n=13) vs. non-ALAL (n=16) clinical characteristics and treatment outcome and found no significant difference in age at leukemia diagnosis, presenting white blood cell count, hemoglobin, and platelet count, or marrow blast percentage between ALAL and non-ALAL patients. Significantly more ALAL patients were treated with acute myeloid leukemia (AML) based regimens (70%) than non-ALAL patients (12.5%) (p= 0.0016), since 14 of 16 non-ALAL cases were ALL with aberrant myeloid marker expression at re-review. Patients classified as ALAL (n=13) demonstrated a trend to worse overall survival than non-ALAL patients (median 12.25 vs. 20 months, p=0.08) (Figure 1) and potentially worse overall survival following AML than ALL therapy (median 14 vs 17 months, p=0.38). The ALAL patients with the longest survival following AML induction chemotherapy (i.e. 70.6, 27.1, and 17 months) were those who underwent subsequent allogeneic stem cell transplantation. This was not true in the non-ALAL patients and ALAL patients treated with ALL regimens where long-term survival was achieved following chemotherapy in the absence of transplantation. Among all 29 patients identified here, administration of ALL-based chemotherapy independent of EGIL/WHO classification was significantly associated with improved overall survival (p=0.015) (Figure 2).Figure 1.Figure 1. Figure 2.Figure 2. In summary, this single institution retrospective review shows that 2008 WHO classification simplifies the diagnosis and limits the number of ALAL/MPAL compared to EGIL score system but this rare entity remains a diagnostic challenge. Over half of these 29 cases preliminarily diagnosed as acute leukemia with dual or uncertain lineage were re-classified as ALL. Although limited by small patient numbers, our preliminary findings suggest that patients diagnosed with ALAL using either EGIL or WHO criteria fare worse than non-ALAL patients and achieve better outcomes (in the absence of allogeneic stem cell transplantation) following ALL-based chemotherapy. Given the overall difficulty in assigning ALAL vs. non-ALAL diagnoses based on EGIL vs. WHO criteria, our results support the upfront treatment of AL of unclear lineage with ALL-based chemotherapy regimens. Disclosures: No relevant conflicts of interest to declare.
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.
