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

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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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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: bronze
doi.org
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 › Hematology › 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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