RARE DISEASE
Myeloproliferative neoplasm
Myeloproliferative neoplasm
Myeloproliferative neoplasm
Synonyms: MPD, MPN, Myeloproliferative disorder
Synonyms: MPD, MPN, Myeloproliferative disorder
Synonyms: MPD, MPN, Myeloproliferative disorder
Drug discovery
3
drugs
With orphan designations
Overview
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by excessive production of mature blood cells, often driven by mutations in JAK2, CALR, or MPL genes. They include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), with rare progression to acute myeloid leukemia (AML) [1][2][7]. Chronic inflammation and symptom burden are hallmarks, necessitating tailored therapies [5][9].
Therapies
Symptom control: Phlebotomy (PV), ruxolitinib (JAK1/2 inhibitor), hydroxyurea, interferon-α [1][2][8].
Curative: Allogeneic stem cell transplant (limited by age/comorbidities) [3][17].
Emerging: Imetelstat (telomerase inhibitor), CALR-targeted vaccines, and combination therapies in trials [3][8][16].
Categories: rare hematological diseases, rare neoplastic diseases, rare transplant-related disorders
Research Papers
3,159 drug discovery papers about Myeloproliferative neoplasm, with 6 first-in-class and 46 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
3,159 drug discovery papers about Myeloproliferative neoplasm, with 6 first-in-class and 46 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-17 | Choreiform Movements and Pachymeningeal Enhancement in an Elderly Patient With Abnormal Blood Counts: A Case Report and Review of Literature.
Polycythemia vera (PV) is a clonal myeloproliferative neoplasm primarily caused by the JAK2V617F mutation, present in 95% of patients. It results in erythropoietin-independent hematopoietic proliferation, erythrocytosis, increased hematocrit (Hct), leukocytosis, thrombocytosis, and hyperviscosity, predisposing patients to thrombotic events and neurologic deficits, including erythromelalgia and pruritus. Neurologic manifestations can occur, such as transient ischemic attack (TIA) and stroke. We report an 83-year-old woman, PV patient who presented with chorea and magnetic resonance imaging (MRI) of her brain showed pachymeningeal enhancement (dural-arachnoid enhancement); this radiological finding is most commonly described in intracranial hypotension, autoimmune conditions, infection, and neoplastic processes and has not been reported in PV. Laboratory findings included complete blood count (CBC) showed severe erythrocytosis, moderate leukocytosis with moderate, mild thrombocytosis; bone marrow (BM) aspiration and biopsy showed hypercellular BM and marked megakaryocytic hyperplasia; and positive JAK2V617F mutation with 80% JAK2 DNA, suggestive of PV as the underlying cause. The patient underwent phlebotomy and was started on Aspirin. Following treatment, she showed dramatic improvement in choreiform movements. Hydroxyurea 500 mg three times daily was subsequently added, leading to complete hematologic response and resolution of pachymeningeal thickening on follow up MRI. This case suggested association between polycythemia vera and choreiform movements and a possible mechanism is proposed.
2026-08-13 | Targeting SIRT6 epigenetically restrains neutrophil hyperplasia and enhances chemotherapeutic efficacy.
Myeloproliferative neoplasms (MPNs) are a group of hematologic malignancies for which current treatment options remain limited, underscoring the urgent need to explore novel therapeutic targets and intervention strategies. Through a high-throughput screen of an epigenetic compound library, we identified the SIRT6 allosteric agonist MDL-800 as a potent suppressor of neutrophil hyperplasia. We established an endogenous sirt6-mutant zebrafish model that develops a myeloproliferative neoplasm (MPN)-like phenotype, with a 64% incidence in adult zebrafish. Mechanistically, Sirt6 was found to regulate neutrophil proliferation in vivo and in vitro by deacetylating histone H3K9 at the c-myb promoter. Sirt6 deficiency led to aberrant proliferation of neutrophils and hematopoietic stem/progenitor cells, whereas Sirt6 overexpression significantly alleviated neutrophil hyperplasia and MPN-related symptoms. Furthermore, the SIRT6 activator MDL-800 enhanced the efficacy of imatinib and reduced neutrophil proliferation in a zebrafish leukemia model. In xenograft mouse models, the combination of MDL-800 and imatinib significantly inhibited leukemia progression and restored drug sensitivity in imatinib-resistant cases. This study establishes the Sirt6-c-Myb axis as a core epigenetic pathway for myeloid homeostasis, providing a novel strategy for simultaneously suppressing neutrophil hyperplasia and enhancing chemotherapeutic efficacy in hematologic malignancies.
2026-08-12 | A patient with myelodysplastic/myeloproliferative neoplasm with neutrophilia (MDS/MPN-N) harboring a DDX41 germline mutation: a case report.
We report a 39-year-old male with MDS/MPN with neutrophilia harboring a germline DDX41mutation. Next sequencing revealed mutational redundancy, wherein high-risk somatic lesions (ASXL1, SRSF2) may contribute to disease evolution in lieu of a detectable DDX41second hit. Despite a favorable karyotype, the patient relapsed early after the first allogeneic hematopoietic stem cell transplantation (allo-HSCT). He achieved remission via venetoclax/azacitidine(VA) bridging followed by a second allo-HSCT. This case expands the phenotypic spectrum of DDX41and underscores that allo-HSCT remains the definitive curative strategy, irrespective of non-transplant response rates or conventional risk models.
2026-08-10 | A Rare BCR::SPECC1L::ABL1 Fusion in a Pediatric Chronic Myeloid Leukemia Patient.
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm typically defined by BCR::ABL1 p210 fusions isoforms. An 8-year-old female CML patient harbored a typical t(9;22)(q34;11) Philadelphia chromosome and BCR::ABL1 fusion by conventional karyotyping and FISH but lacked BCR::ABL1 p210 fusion transcripts by RT-PCR. Targeted next-generation sequencing (NGS) revealed BCR::SPECC1L::ABL1 fusion transcripts predicted to encode an in-frame BCR-exon-8::SPECC1L-exon-4::ABL1-exon-2 fusion protein retaining the tyrosine kinase domain. FISH and NGS were used for therapeutic imatinib monitoring given this atypical isoform. This case highlights the role of multimodal molecular diagnostics to diagnose and monitor pediatric CML patients with atypical fusion isoforms.
2026-08-04 | Emerging agents and regimens for myeloproliferative neoplasms: updates from ASH 2025 Annual Meeting.
Current Myeloproliferative neoplasm (MPN) therapies provide meaningful symptom and event-risk control but are limited by infrequent molecular remissions, treatment-limiting cytopenias (particularly anemia), and continued reliance on non-mutation-directed cytoreduction or phlebotomy with attendant morbidity. At ASH 2025 Annual Meeting, multiple investigational strategies aimed to address these limitations, including clone-directed targeting (INCA033989), phlebotomy-sparing physiologic therapy (rusfertide), and epigenetic disease-modifying combinations (pelabresib). We summarized the latest updates on these emerging agents and regimens for MPNs from the 2025 ASH Annual Meeting.
2026-08-17 | Choreiform Movements and Pachymeningeal Enhancement in an Elderly Patient With Abnormal Blood Counts: A Case Report and Review of Literature.
Polycythemia vera (PV) is a clonal myeloproliferative neoplasm primarily caused by the JAK2V617F mutation, present in 95% of patients. It results in erythropoietin-independent hematopoietic proliferation, erythrocytosis, increased hematocrit (Hct), leukocytosis, thrombocytosis, and hyperviscosity, predisposing patients to thrombotic events and neurologic deficits, including erythromelalgia and pruritus. Neurologic manifestations can occur, such as transient ischemic attack (TIA) and stroke. We report an 83-year-old woman, PV patient who presented with chorea and magnetic resonance imaging (MRI) of her brain showed pachymeningeal enhancement (dural-arachnoid enhancement); this radiological finding is most commonly described in intracranial hypotension, autoimmune conditions, infection, and neoplastic processes and has not been reported in PV. Laboratory findings included complete blood count (CBC) showed severe erythrocytosis, moderate leukocytosis with moderate, mild thrombocytosis; bone marrow (BM) aspiration and biopsy showed hypercellular BM and marked megakaryocytic hyperplasia; and positive JAK2V617F mutation with 80% JAK2 DNA, suggestive of PV as the underlying cause. The patient underwent phlebotomy and was started on Aspirin. Following treatment, she showed dramatic improvement in choreiform movements. Hydroxyurea 500 mg three times daily was subsequently added, leading to complete hematologic response and resolution of pachymeningeal thickening on follow up MRI. This case suggested association between polycythemia vera and choreiform movements and a possible mechanism is proposed.
2026-08-13 | Targeting SIRT6 epigenetically restrains neutrophil hyperplasia and enhances chemotherapeutic efficacy.
Myeloproliferative neoplasms (MPNs) are a group of hematologic malignancies for which current treatment options remain limited, underscoring the urgent need to explore novel therapeutic targets and intervention strategies. Through a high-throughput screen of an epigenetic compound library, we identified the SIRT6 allosteric agonist MDL-800 as a potent suppressor of neutrophil hyperplasia. We established an endogenous sirt6-mutant zebrafish model that develops a myeloproliferative neoplasm (MPN)-like phenotype, with a 64% incidence in adult zebrafish. Mechanistically, Sirt6 was found to regulate neutrophil proliferation in vivo and in vitro by deacetylating histone H3K9 at the c-myb promoter. Sirt6 deficiency led to aberrant proliferation of neutrophils and hematopoietic stem/progenitor cells, whereas Sirt6 overexpression significantly alleviated neutrophil hyperplasia and MPN-related symptoms. Furthermore, the SIRT6 activator MDL-800 enhanced the efficacy of imatinib and reduced neutrophil proliferation in a zebrafish leukemia model. In xenograft mouse models, the combination of MDL-800 and imatinib significantly inhibited leukemia progression and restored drug sensitivity in imatinib-resistant cases. This study establishes the Sirt6-c-Myb axis as a core epigenetic pathway for myeloid homeostasis, providing a novel strategy for simultaneously suppressing neutrophil hyperplasia and enhancing chemotherapeutic efficacy in hematologic malignancies.
2026-08-12 | A patient with myelodysplastic/myeloproliferative neoplasm with neutrophilia (MDS/MPN-N) harboring a DDX41 germline mutation: a case report.
We report a 39-year-old male with MDS/MPN with neutrophilia harboring a germline DDX41mutation. Next sequencing revealed mutational redundancy, wherein high-risk somatic lesions (ASXL1, SRSF2) may contribute to disease evolution in lieu of a detectable DDX41second hit. Despite a favorable karyotype, the patient relapsed early after the first allogeneic hematopoietic stem cell transplantation (allo-HSCT). He achieved remission via venetoclax/azacitidine(VA) bridging followed by a second allo-HSCT. This case expands the phenotypic spectrum of DDX41and underscores that allo-HSCT remains the definitive curative strategy, irrespective of non-transplant response rates or conventional risk models.
2026-08-10 | A Rare BCR::SPECC1L::ABL1 Fusion in a Pediatric Chronic Myeloid Leukemia Patient.
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm typically defined by BCR::ABL1 p210 fusions isoforms. An 8-year-old female CML patient harbored a typical t(9;22)(q34;11) Philadelphia chromosome and BCR::ABL1 fusion by conventional karyotyping and FISH but lacked BCR::ABL1 p210 fusion transcripts by RT-PCR. Targeted next-generation sequencing (NGS) revealed BCR::SPECC1L::ABL1 fusion transcripts predicted to encode an in-frame BCR-exon-8::SPECC1L-exon-4::ABL1-exon-2 fusion protein retaining the tyrosine kinase domain. FISH and NGS were used for therapeutic imatinib monitoring given this atypical isoform. This case highlights the role of multimodal molecular diagnostics to diagnose and monitor pediatric CML patients with atypical fusion isoforms.
2026-08-04 | Emerging agents and regimens for myeloproliferative neoplasms: updates from ASH 2025 Annual Meeting.
Current Myeloproliferative neoplasm (MPN) therapies provide meaningful symptom and event-risk control but are limited by infrequent molecular remissions, treatment-limiting cytopenias (particularly anemia), and continued reliance on non-mutation-directed cytoreduction or phlebotomy with attendant morbidity. At ASH 2025 Annual Meeting, multiple investigational strategies aimed to address these limitations, including clone-directed targeting (INCA033989), phlebotomy-sparing physiologic therapy (rusfertide), and epigenetic disease-modifying combinations (pelabresib). We summarized the latest updates on these emerging agents and regimens for MPNs from the 2025 ASH Annual Meeting.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
3 orphan drug designations for Myeloproliferative neoplasm.
3 orphan drug designations for Myeloproliferative neoplasm.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Adenosine triphosphate type 1 competitive inhibitor of JAK2 V617F tyrosine kinase | small molecules | FDA | 2011-03-03 | — | Eli Lilly and Company |
pomalidomide | small molecules | FDA | 2010-09-21 | — | Celgene Corporation |
lestaurtinib | small molecules | FDA | 2009-09-03 | — | Teva Branded Pharmaceutical Products R&D, Inc. |
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