Abstract
Essential thrombocythemia (ET) is a myeloproliferative disorder associated with megakaryocytic hyperplasia and thrombocytosis. In this disease, in vitro autonomous growth of megakaryocytic colonies has been demonstrated by various investigators. This phenomenon is impaired by the inhibition of the thrombopoietin/c-mpl pathway. In order to evaluate the potential role of mutations of the receptor gene in the origin of this autonomous growth, we compared the expression of c-mpl mRNA isoforms in platelets derived from ET patients and normal subjects. Overlapping c-mpl PCR fragments derived from four ET patients were sequenced to search for small mutations. In the 10 ET and five normal samples we studied, relative expression of the c-mpl isoforms was identical. New variants of Mpl-P and K isoforms, Mpl-P2 and K2 were detected. Cloning of these isoforms indicated that they are produced by alternative splicing of exon 9 sequences shared by Mpl-P and K. Their predicted amino acid sequence would be deleted by 24 aminoacids, upstream of the WSSWS box of the second domain of c-mpl. Two sequence variations, leading to DNA restriction polymorphisms, were present in the extracellular and Mpl-K intracytoplasmic domains. Both were present in normal and ET samples, excluding mutations of c-mpl as a cause of ET.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kiladjian, J., Elkassar, N., Hetet, G. et al. Study of the thrombopoietin receptor in essential thrombocythemia. Leukemia 11, 1821–1826 (1997). https://doi.org/10.1038/sj.leu.2400845
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.leu.2400845
Keywords
This article is cited by
-
c-Mpl-del, a c-Mpl alternative splicing isoform, promotes AMKL progression and chemoresistance
Cell Death & Disease (2022)
-
Constitutively activated phosphatidylinositol 3-kinase primes platelets from patients with chronic myelogenous leukemia for thrombopoietin-induced aggregation
Leukemia (2004)
-
Nuclear factor-erythroid 2 (NF-E2) expression in normal and malignant megakaryocytopoiesis
Leukemia (2002)
-
Basic sciences of the myeloproliferative diseases: Pathogenic mechanisms of ET and PV
International Journal of Hematology (2002)
-
The Pathogenesis of Chronic Myeloproliferative Diseases
International Journal of Hematology (2001)