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Cited by 642Platelet Disorders and TreatmentsBlood Coagulation and Thrombosis MechanismsMyeloproliferative Neoplasms: Diagnosis and Treatment

Thrombopoietin: the primary regulator of platelet production [see comments]

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Kaushansky, K·1995·Blood
DOI 10.1182/blood.v86.2.419.bloodjournal862419
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Abstract

CONCEPT was advanced some 37 years ago, evidence for the existence of a humoral regulator of platelet production, first termed thrombopoietin (Tpo) by Kelemen et al,' accumulated very slowly.Initial studies in the 1960s and 1970s indicated that thrombocytopenia evokes characteristic marrow changes including increases in the number, size, ploidy, and maturation rate of megakaryocyte^.^"Platelet transfusion-induced thrombocytosis was associated with the opposite effects.*These findings were later confirmed with the availability of improved methods of assessing cellular DNA content and megakaryocyte maturation.'"'Ode11 et allz are generally acknowledged as providing the first description of a humoral substance in the sera of thrombocytopenic rats which induced thrombocytosis in recipient animals.Subsequent investigators have reported that thrombocytopenic serum also induces many of the marrow effects associated with thromb~cytopenia.'~"~However, significant progress in the field awaited the development of reliable, albeit cumbersome, assays of Tpo activity.I7-*' Attempts to biochemically purify Tpo from plasma, serum, urine, and conditioned culture medium from various cell lines occupied much effort during the 1 9 8 0 ~.~" ~~ Unfortunately, because of the complex nature of the starting material and difficulties associated with the use of an in vivo assay, these attempts failed to yield homogeneous protein adequate for protein sequencing and cDNA cloning, the official rite of passage for a hematopoietic growth factor.Furthermore, a number of cytokines were described in the late 1980s and early 1990s that possessed activity in various assays of megakaryocyte development.2943During the past several years, many investigators suggested that a distinct, lineage-specific thrombopoietin may not exist. THE SEARCH FOR TPOFour groups have published extensively on the purification of substances that either augment platelet production or stimulate megakaryocyte development.Levin's group has reported on the biologic effects of Tpo partially purified from thrombocytopenic rabbit plasma.24b27"*45These workers used ammonium sulfate fractionation, two types of lectin affinity chromatography, and gel filtration on high-pressure liquid chromatography (HPLC) columns to obtain material that reproducibly increased platelet production in recipient animals.Its reported molecular weight (M,) was 40 to 47 kD."Additional biologic activities ascribed to partially purified Tpo include augmentation of megakaryocyte ploidy, both in vitro Blood, Voi 86, No 2 (July 15).

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  • Thrombopoietin activates the JAK/STAT3 pathway in megakaryocytes, leading to upregulated expression of multiple genes required for platelet production.

    “Thrombopoietin activates the JAK/STAT3 pathway in megakaryocytes”

    From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Kaushansky, 1995

    The In Vitro Activities of ML section says thrombopoietin supports megakaryocyte maturation and fragmentation into platelets, and The Successful Search Begins describes signaling through its receptor. Neither passage establishes activation of JAK/STAT3 in megakaryocytes; searches for “JAK” and “STAT3” found no such passage. The supplied claim’s additional assertion about upregulated platelet-production genes is also not established by these passages. (LLM, conf=0.82)

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Research works printed but not linked: 2

  1. Shivdasani RA, Rosenblatt M F , Vignali K, Zucker-Franklin D, Jackson CW, Hunt P, Saris CJM, Orkin SH: Transcription factor NF-E2 is required for platelet formation independent of the actions SUPPl 1) of thrombopoietin/MGDF in megakaryocyte development. Cell (in press) 106.
  2. Geissler K, Stockenhuber F, Hinterberger W, Balcke B, Lechner K Recombinant human erythropoietin: A multipotential hemopoietic growth factor in vivo and in vitro, in Schaefer RM, Heidland A, Horl WH (eds): Erythropoietin in the 90s. Contributions to Nephrology, v01 87. Basel, Switzerland, Karger, 1990, p 1 142. Moore MAS, Warren DJ: Synergy of interleukin-l and gran- ulocyte colony-stimulating factor: In vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice. Proc Natl Acad Sci USA 84:7134, 1987 143.

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Authors
Kaushansky, K.
Corresponding author
Kaushansky, K
Venue
Blood
Publisher
American Society of Hematology
Published
1995-07-15
Volume
86
Issue
2
Pages
419-431
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v86.2.419.bloodjournal862419
OpenAlex
W2230842386
Cited by
642
References
103
Citations by year
2026: 6 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 7 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 13 · 2016: 13 · 2015: 8 · 2014: 15 · 2013: 5 · 2012: 10
FWCI
39.31
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Genetics › Myeloproliferative Neoplasms: Diagnosis and Treatment
Keywords
thrombopoietin, megakaryopoiesis, megakaryocyte development, thrombocytopenia, thrombocytosis, hematopoietic growth factors, thrombopoietin receptor, cDNA cloning, protein purification, cytokines, megakaryocyte maturation, platelet transfusion
MeSH terms
Animals, Blood Platelets, Cell Division, Gene Expression Regulation, Genes, Hematopoiesis, Humans, Megakaryocytes, Mice, Inbred BALB C, Radiation Injuries, Experimental, Receptors, Immunologic, Thrombocytopenia, Thrombopoietin, Carboplatin, Mice

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