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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-05-1553.

Submitted May 28, 2002
Accepted August 21, 2002
Megakaryocyte polyploidization is associated with a functional gene amplification
Hana Raslova, Lydia Roy, Claire Vourc'h, Jean P LeCouedic, Olivier Brison, Didier Metivier, Jean Feunteun, Guido Kroemer, Najet Debili, and William Vainchenker*
Institut Gustave Roussy PR-1, INSERM Unite 362, Villejuif Cedex, France
Institut Albert Bonniot, INSERM Unite 309, La Tronche, France
Institut Gustave Roussy, CNRS UMR.1599, Villejuif Cedex, France
* Corresponding author; email: verpre{at}igr.fr.
It is believed that polyploidy induces an orchestrated increase in gene expression. To know whether all alleles remain functional during megakaryocyte polyploidization, we used a well-established FISH technique which allows one to simultaneously detect pre-mRNAs and assess ploidy level in a single cell. All alleles of GPIIb, GPIIIa, vWF, ß-actin, hsp70, c-mpl, Fli-1 and FOG-1 genes are transcriptionally active in megakaryocytes from 4N to 32N. All X chromosomes in male cells but only half of them are transcriptionally active in female megakaryocytes, as revealed by the transcriptional activity of the GATA-1 gene. Nuclear untranslated XIST RNA accumulates on the inactivated X chromosomes, indicating that they are subjected to a normal inactivation process. Altogether, our results demonstrate that megakaryocyte polyploidization results in a functional gene amplification whose likely function is an increase in protein synthesis in parallel to cell enlargement.

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