DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Pelger-Huet anomaly — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePelger-Huet anomaly maps to a 1-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 pelger-huet anomaly 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.
What the evidence adds up to
Pelger-Huët anomaly is an autosomal dominant haematological trait characterised by neutrophil nuclear hypolobulation and modified chromatin distribution, caused by mutations in the lamin B receptor gene. It is a rare benign disorder that does not cause a defect in the immune system, and is often overlooked because it is asymptomatic or because observers are unfamiliar with it. The morphological change can also be seen in other leukocytes, especially eosinophils. It must be distinguished clinically from pseudo-Pelger-Huët anomaly, which has very similar morphologic characteristics but is associated with different pathological states.
Acquired Pelger-Huët anomaly has been reported in association with both haematologic and nonhaematologic diseases, including myeloid haematologic disorders, chronic lymphocytic leukaemia, multiple myeloma, Hodgkin’s disease, and non-Hodgkin’s lymphoma. In one 1996 study, 23 patients treated with taxoid therapy—13 with paclitaxel and 10 with docetaxel—developed transient acquired Pelger-Huët anomaly. A consistent peak of Pelger-Huët cells occurred 3 to 9 days after treatment, and the anomaly generally disappeared by day 21. Peak Pelger-Huët cell counts for the first course were significantly different between paclitaxel, docetaxel, and control groups (P < 0.0001), with docetaxel producing significantly higher maximum counts than paclitaxel (P < 0.001), and paclitaxel producing significantly higher counts than controls (P = 0.007).
A 2024 case report describes a 22-year-old woman whose Pelger-Huët anomaly was noticed on peripheral smear after she came to a haematology clinic because her sibling had Hodgkin’s lymphoma. Family members were also evaluated. A 2009 review notes that the anomaly is often overlooked due to its asymptomatic nature or lack of observer familiarity, and that a comprehensive approach to assessment of this laminopathy is important. Unfamiliarity with the appearance of mature neutrophils with bilobed nuclei and coarse chromatin clumping can lead to erroneous classification, and Pelger-Huët cells might be mistaken for a left shift.
What is still missing is any evidence that the inherited form requires treatment—it is benign and asymptomatic—and no therapy has been tested in a controlled trial. For the acquired form, the only documented drug association is with taxoids, and that is a transient, reversible effect, not a treatment. No drug has been studied for reversing or preventing the inherited anomaly, and no patient stratification or trial design exists for that purpose.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Acta Haematologica · 2009 · 34 citations
Pelger-Huët Anomaly: A Critical Review of the Literature
AbstractPelger-Huët anomaly (PHA), an autosomal dominant haematological trait is characterised by neutrophil nuclear hypolobulation and modified chromatin distribution. Mutations in the lamin B receptor gene, a member of the sterol reductase family have been identified as the underlying cause. Due to its asymptomatic nature or lack of observer familiarity, PHA is often overlooked. In this review, we give an overview of the main pathophysiological, clinical, morphological and functional aspects of PHA. Furthermore, we highlight the importance of a comprehensive approach to the assessment of this laminopathy.
British Journal of Haematology · 1996 · 30 citations · open access
Association of acquired Pelger‐Huet anomaly with taxoid therapy
AbstractWe describe the occurrence of acquired Pelger-Huet anomaly (APHA) in 23 patients treated with paclitaxel (13) or docetaxel (10). A consistent peak of Pelger-Huet cells (PHC) within a range of 3-9 d after treatment with taxoids was noted. The APHA generally disappeared by day 21 after treatment. Peak PHC values for the first course were significantly different in paclitaxel versus docetaxel versus control groups (P < 0.0001) with the maximum PHC counts being significantly higher for docetaxel compared with paclitaxel (P < 0.001) and for paclitaxel compared with controls (P = 0.007). We conclude that taxoid therapy produces transient APHA which peaks between days 3 and 9 and is more pronounced with docetaxel than with paclitaxel.
Acquired Pelger-Huet Anomaly in a Case of Non-Hodgkin’s Lymphoma
AbstractAcquired Pelger-Huet anomaly has been found in association with both hematologic and nonhematologic diseases. While its association with myeloid hematologic disorders is well known, this granulocytic anomaly has also been found in chronic lymphocytic leukemia, multiple myeloma and Hodgkin's disease. This report describes a case of acquired Pelger-Huet anomaly in non-Hodgkin's lymphoma and reviews the association of this anomaly with both lymphoid and myeloid hematologic disorders.
Oxford Medical Case Reports · 2015 · 7 citations · open access
Case of acquired or pseudo-Pelger-Huet anomaly
AbstractPelger-Huët anomaly (PHA) is a rare benign autosomal-dominant anomaly with an incidence of ∼1 in 6000. It does not cause neutrophilia, but it can cause a false increase in band forms. It should be differentiated from acquired or pseudo-Pelger-Huët anomaly (PPHA), which has similar morphology, however; it is associated with different pathological states like Myelodysplastic syndrome, as well as with certain infections and drugs. We report a case of a 67-year-old Caucasian gentleman with past medical history of rheumatoid arthritis, type II diabetes mellitus and hypothyroidism, who presented with 1 day history of fever (101°F) and night sweats. Medications include ibuprofen, methotrexate, hydroxychloroquine and levothyroxine. Patient denied any other symptoms. His work-up showed normal WBC count (8.6) and increase in bands (24%). The patient was admitted for further evaluation. During the next 2 days, the patient did not have any fever or any new symptoms. Peripheral blood smear was done as part of his work-up for bandemia, showed findings suggestive of PHA. Ibuprofen was discontinued. Follow-up few weeks later showed normal blood smear. Diagnosis of PPHA was made. The presented case showed that we should think of PHA\PPHA in any case with normal total WBC count and significant shift to the lift with no apparent explanation. Looking at smears directly under the microscopes is crucial to make diagnosis.
AbstractPelger-Huët anomaly is a rare benign hematological disorder. It was first described in the 1920s. It is inherited in an autosomal dominant manner. Nuclear hypolobulation, which can also be seen in other leukocytes, especially neutrophils, is a characteristic feature. This morphological change does not cause a defect in the immune system. It should be differentiated clinically from pseudo-Pelger-Huët anomaly (PPHA). In this study, Pelger-Huët anomaly is presented which is noticed in the peripheral smear of a 22-year-old female patient who came to the hematology outpatient clinic due to her sibling having Hodgkin’s lymphoma. The family members of the case were also evaluated in this respect.
Hematology & Transfusion International Journal · 2017 · 0 citations · open access
Inherited Disorder: Pelger-Huët Anomaly
AbstractUnfamiliarity with the appearance of immature neutrophils and mature neutrophils with bilobed nuclei and coarse clumping of the nuclear chromatin can lead to their erroneous classification. Presence of Pelger-Hut cells might be mistaken for a shift to the left, which represents an increase in the number of un-segmented (band) neutrophils in the circulation. Pelger-Hut anomaly, rather rare disorder is an inherited failure of the nuclei of neutrophils (and also eosinophils) to mature to the normal segmented form. PHA occurs secondary to mutations in the lamin B receptor. Consequently, a left shift always appears to be present. However, distinguishing PHA with acquired or pseudo-Pelger-Hut anomaly (PPHA), which has very similar morphologic characteristics, but it is associated with different pathological states, is very important.
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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