DeCure for Acute myeloid leukemia, t(3;5)(q25;q34)
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for acute myeloid leukemia, t(3;5)(q25;q34) — 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 moduleAcute myeloid leukemia, t(3;5)(q25;q34) 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
approvedPonatinibApproved drug
Structures already discussed alongside acute myeloid leukemia, t(3;5)(q25;q34) in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance — Ponatinib has a real, experimentally solved structure in complex with this target (PDB 3IK3, 1.9 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet 0lidrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3IK3 · 1.9 Å · ligand Ponatinib (0LI). Experimental structure, not a prediction.
What the evidence adds up to
A phase 4 study of nilotinib in 110 Korean patients with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase reported a 24-month cumulative MR4.5 rate of 56.2% (95% confidence interval, 44.0%–8.3%) and a median time to MR4.5 of 23.3 months. One patient died from acute viral hepatitis, two developed haematological or cytogenetic relapse, and no progression to accelerated or blast phase was observed. Plasma nilotinib concentrations showed no predictive value for patient outcomes. A separate real-world study of 118 patients with chronic myeloid leukaemia treated with imatinib found that 50% experienced at least one dosage modification event during the first year, with 52% of those events occurring in the first six months. Dosage modifications were associated with a reduced likelihood of achieving a 6-month molecular response milestone (p < 0.05), but not with outcomes at 3 or 12 months. The authors noted limitations including sample size and lack of adjustment for multiple comparisons.
A Belgian registry reported final 6-year results for ponatinib in 54 patients with chronic myeloid leukaemia and 29 with Philadelphia chromosome-positive acute lymphoblastic leukaemia. Median follow-up was 545 days for CML and 258 days for Ph+ ALL. Best response to ponatinib was at least a major molecular response in 65% of CML and 55% of Ph+ ALL patients. Overall survival was 85.8% at 48 months in CML and 82.5% at 30 months in Ph+ ALL; progression-free survival was 83.8% and 54.2%, respectively. Adverse reactions occurred in 85% of CML and 76% of Ph+ ALL patients, with cardiovascular events in 33% and 24%. The authors stated these real-world data support use of ponatinib in patients with resistance or intolerance to previous TKIs or carrying the T315I mutation.
A 2024 review article on acute myeloid leukaemia noted that despite recent approvals of targeted therapies by European and American drug agencies, mortality remains very high, particularly in relapsed or refractory patients. A 1993 report described four cases of de novo acute leukaemia with a sole 5q- deletion (q22q33), three of which had proliferation of immature blast cells. A 2023 case report described a 13-year-old boy with AML1-ETO positive acute myeloid leukaemia whose peripheral blood and bone marrow images resembled chronic myelogenous leukaemia, with a white blood cell count of 142.6 x 10⁹/L and primitive cells accounting for 5% in peripheral blood and 17% in bone marrow. The karyotype showed t(8;21)(q22;q22). The authors emphasised that cytogenetics and molecular genetics are essential for diagnosis.
What is still missing for the specific disease t(3;5)(q25;q34) acute myeloid leukaemia is any dedicated clinical trial data, patient stratification by molecular subtype, and funding to study this rare translocation directly. The abstracts provided do not address this cytogenetic abnormality.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer Medicine · 2018 · 14 citations · open access
A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: <scp>ENESTK</scp>orea
AbstractAbstract Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events ( AE s) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase ( CML ‐ CP ). We investigated the 2‐year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations ( PNC s). In this open‐label, multi‐institutional phase 4 study, 110 Philadelphia chromosome‐positive CML ‐ CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses ( MR s) and AE s were monitored for up to 24 months. The 24‐month cumulative MR 4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNC s, and the per‐patient mean was used to categorize them into four mean PNC ( MPNC ) groups. Cumulative MR rates and safety were compared between groups. With a median follow‐up of 22.2 months, the 24‐month cumulative MR 4.5 rate was 56.2% (95% confidence interval, 44.0%–8.3%), and the median time to MR 4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR 4 , and MR 4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AE s. Nilotinib is highly effective for the treatment of CML ‐ CP with manageable AE s. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT 03332511.
ETO sequence may be dispensable in some AML1-ETO leukemias
AbstractAcute myeloid leukemia (AML) is a heterogeneous disease, with individual cases showing variability in clinical presentation, blast-cell morphology, therapeutic response, and long-term prognosis. One of the most common cytogenetic abnormalities described in AML is t(8;21)(q22;q22) found in 10% to 15
Leukemia & lymphoma/Leukemia and lymphoma · 1993 · 4 citations
De Novo Acute Leukemia with a Sole 5q-: Morphological, Immunological, and Clinical Correlations
AbstractThe 5 q deletion is frequently found in myelodysplastic syndromes and acute non lymphoid leukemia, but this anomaly is usually found in secondary diseases and associated with many other chromosomal aberrations. This report describes four cases of "de novo" acute leukemia with a sole 5q- anomaly. They had no cytological, genetic or clinical characteristics of secondary disorders. It is important to note that of the four patients studied, three had proliferation of immature blast cells. One case was classified as a MO AML and two as "undifferentiated" acute leukemia. Furthermore, these four cases of acute leukemia showed a deletion of the same portion of the long arm of chromosome 5: q22q33. On the same part of this chromosome many hematopoietic growth factor genes have been located, like IL3 and GM-CSF which have early undifferentiated hematopoietic stem cells as a their target.
Unveiling the Role of New Molecules in Acute Myeloid Leukemia: Insights into Disease Pathogenesis and Therapeutic Potential
AbstractThis review article explores the current landscape of acute myeloid leukemia treatment, including novel target molecules and recent advancements in cell therapy and immunotherapy focused on T cell activity. Advances in treatment have been promising in recent years, driven by the development of therapies targeting new molecular and genetic therapeutic targets. These findings allowed for the approval of several target therapies by the European and American drug agencies in the last 5 years. However, mortality remains very high, particularly in relapsed or refractory (R/R) patients. In recent years, the development of immunotherapy has expanded this field, leading to the introduction of new drugs and treatments.
Prevalence of dosage modifications and impact on response milestone among patients with CML treated with imatinib using RWD.
Abstracte23335 Background: Continuous treatment with BCR-ABL1 TKIs are the cornerstone of chronic myeloid leukemia (CML) treatment. This study aims to assess the prevalence of TKI dosage modifications, including interruptions and reductions, and their impact on treatment effectiveness. Methods: This retrospective observational study utilized the UNC Clinical Data Warehouse electronic health record (EHR) database. Eligible patients include adults (≥18 years) diagnosed with CML receiving imatinib as first-line therapy for >1 month between 2010-2023. Patients with incomplete dosing data were excluded. Descriptive statistics include the types and prevalence of dosage modifications, including dose reduction, dosage interruption, and drug discontinuation. Efficacy analyses were evaluated using BCR-ABL transcripts and early response milestones at 3, 6, and 12 months. Statistical analyses were performed using Fisher’s exact test, with a two-sided α level of 0.05. Results: A total of 118 patients were included with a median age of 61 years, mostly female (55%), and racially diverse (59% White; 26% Black; 2% Asian; 1% American Indian; 7% Hispanic; 5% Other/Unknown). Of these patients, 59 patients (50%) experienced a total of 112 all-cause dosage modification events during the first year of use: dose reductions (26%), dosage interruptions (46%), dose discontinuations (25%), and others (3%). Fifty-two percent (58/112) of dose modification events occurred in the first 6 months. Additionally, 39 patients (66%) experienced dosage modifications due to toxicities, while 4 patients (3%) initiated treatment at a reduced dose of imatinib. Among the patients with evaluable response data, 54/84 (64%) patients achieved an early molecular response (BCR-ABL <10%) at month 3, 48/72 (67%) patients achieved <1% at month 6, and 39/67 (58%) patients achieved <0.1% at month 12. Dosage modifications were associated with reduced likelihood of achieving 6-month milestones (p < 0.05) but were not significantly associated with outcomes at 3 (p =0.33) or 12 months (p = 0.52). Conclusions: We demonstrated the feasibility of leveraging a complex EHR data source from an integrated health system to study the impact of dose modifications on clinical outcomes for self-administered chemotherapy. Nearly half of the patients in our study cohort experienced dosage modifications. While these modifications were associated with a lower likelihood of achieving 6-month molecular response milestones, this finding has various limitations due to the sample size, retrospective nature, and lack of adjustment for multiple comparisons in this study. Our cohort of patients experienced more treatment discontinuations due to toxicities when compared to clinical trials. Additional analyses are needed to further evaluate the long-term impact and causal effect of dosage modifications due to toxicities on clinical outcomes.
A Case of AML1-ETO Positive Acute Myeloid Leukemia Morphologically Similar to Chronic Myelogenous Leukemia
AbstractBACKGROUND: The goal was to study the role of the morphology, immunophenotype, karyotype and fusion gene expression in a patient with diagnosis of AML1-ETO positive acute myeloid leukemia. METHODS: A case of AML1-ETO positive acute myeloid leukemia morphologically similar to chronic myelogenous leukemia was reported. The results of the morphology, immunophenotype, karyotype and fusion gene expression were analyzed by reviewing relevant literature. RESULTS: The patient was a young boy, at the age of 13, with clinical manifestations of intermittent fatigue and fever. Blood routine: White blood cell 142.6 x 109/L, Red blood cell 0.89 x 1012/L, Hemoglobin 41 g/L, Platelet 23 x 109/L, primitive cells account for 5%. Bone marrow smear: Granulocyte system hyperplasia is obvious, visible at each stage, primitive cells account for 17%, eosinophils, basophils, and phagocytic blood cells were observed. Flow cytometry showed myeloid primitive cell population was 4.14%, immature and mature granulocytes cell population was 85.22%, and eosinophil cell population was 0.61%. The results showed that the proportion of myeloid primitive cell was high, the expression of CD34 was enhanced, the expression of CD117 was partially absent, the expression of CD38 was weakened, the expression of CD19 was weak, and a few cells expressed CD56, and the phenotype was abnormal. The proportion of granulocyte series increased and the nucleus shifted to the left. The proportion of erythroid series was decreased, and the expression of CD71 was weakened. The results of fusion gene showed AML1-ETO positive. Karyotype analysis showed clonogenic abnormality t(8;21)(q22;q22). CONCLUSIONS: The peripheral blood and bone marrow images of patients with t(8;21)(q22;q22) AML1-ETO positive are the manifestations of chronic myelogenous leukemia, suggesting that cytogenetics and molecular genetics play an irreplaceable role in the diagnosis of acute myeloid leukemia, and the comprehensive diagnostic efficiency is significantly better than that of morphology.
Research Square · 2024 · 0 citations · open access
Real-world outcomes in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia treated with ponatinib – Final 6-year results from a Belgian registry
Abstract<title>Abstract</title> Ponatinib is a third-generation tyrosine kinase inhibitor (TKI) for treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in patients who fail or are intolerant to a second-generation TKI or who carry the <italic>T315I</italic> mutation. This is the final analysis of the Belgian ponatinib registry evaluating use of ponatinib in clinical practice, with data available for up to 6 years after reimbursement. Forty-eight percent of 54 CML and 28% of 29 Ph + ALL patients had received ≥ 3 previous TKIs. Before ponatinib, most patients had already achieved a response, including at least a major molecular response (MMR), in 19% of CML and 17% of Ph + ALL patients. Ponatinib was initiated due to intolerance to previous TKIs in 50% of CML and 41% of Ph + ALL patients. Median follow-up was 545 and 258 days for CML and Ph + ALL patients, respectively. Best response to ponatinib was at least an MMR in 65% of CML and 55% of Ph + ALL patients. Overall and progression-free survival were 85.8% and 83.8% in CML patients after 48 months of treatment, and 82.5% and 54.2% in Ph + ALL patients after 30 months of treatment. Adverse reactions were reported by 85% of CML and 76% of Ph + ALL patients, with 33% of CML and 24% of Ph + ALL patients experiencing cardiovascular events. In line with previously published trials, these real-world data support use of ponatinib in CML and Ph + ALL patients with resistance or intolerance to previous TKIs or carrying the <italic>T315I</italic> mutation. Clinicaltrials.gov identifier: NCT03678454; September 19, 2018
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.
