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The molecular mechanisms that control thrombopoiesis
Kenneth Kaushansky
Kenneth Kaushansky
Published December 1, 2005
Citation Information: J Clin Invest. 2005;115(12):3339-3347. https://doi.org/10.1172/JCI26674.
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Review Series Article has an altmetric score of 16

The molecular mechanisms that control thrombopoiesis

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Abstract

Our understanding of thrombopoiesis — the formation of blood platelets — has improved greatly in the last decade, with the cloning and characterization of thrombopoietin, the primary regulator of this process. Thrombopoietin affects nearly all aspects of platelet production, from self-renewal and expansion of HSCs, through stimulation of the proliferation of megakaryocyte progenitor cells, to support of the maturation of these cells into platelet-producing cells. The molecular and cellular mechanisms through which thrombopoietin affects platelet production provide new insights into the interplay between intrinsic and extrinsic influences on hematopoiesis and highlight new opportunities to translate basic biology into clinical advances.

Authors

Kenneth Kaushansky

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Figure 5

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Genetic alterations in thrombopoietin that lead to enhanced translation ...
Genetic alterations in thrombopoietin that lead to enhanced translation efficiency. The normal thrombopoietin mRNA (light blue) is spliced from 7 exons, of which 3 are shown (A). The numbered initiation codons found in the primary thrombopoietin transcript are shown as within their corresponding ORFs (e.g., the thrombopoietin ORF is dark blue and initiates from AUG8). The sites of mutation that lead to enhanced translation of the thrombopoietin transcript do so (B) by eliminating exon 3 by altered splicing (ΔE3) to create a new thrombopoietin ORF initiated by a highly efficient initiation codon (AUG5); (C) by nonsense mutation, prematurely truncating ORF7, which embeds the normal thrombopoietin ORF; or (D) by shifting the efficiently initiated ORF7 (by a single-nucleotide insertion) to now include the thrombopoietin polypeptide. Adapted with permission from Blood (82).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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