FLI1 monoallelic expression combined with its hemizygous loss underlies Paris-Trousseau/Jacobsen thrombopenia

The Journal of Clinical Investigation
Hana RaslovaR Favier

Abstract

Paris-Trousseau syndrome (PTS; also known as Jacobsen syndrome) is characterized by several congenital anomalies including a dysmegakaryopoiesis with two morphologically distinct populations of megakaryocytes (MKs). PTS patients harbor deletions on the long arm of chromosome 11, including the FLI1 gene, which encodes a transcription factor essential for megakaryopoiesis. We show here that lentivirus-mediated overexpression of FLI1 in patient CD34(+) cells restores the megakaryopoiesis in vitro, indicating that FLI1 hemizygous deletion contributes to the PTS hematopoietic defects. FISH analysis on pre-mRNA and single-cell RT-PCR revealed that FLI1 expression is mainly monoallelic in CD41(+)CD42(-) progenitors, while it is predominantly biallelic in the other stages of megakaryopoiesis. In PTS cells, the hemizygous deletion of FLI1 generates a subpopulation of CD41(+)CD42(-) cells completely lacking FLI1 transcription. We propose that the absence of FLI1 expression in these CD41(+)CD42(-) cells might prevent their differentiation, which could explain the segregation of the PTS MKs into two subpopulations: one normal and one composed of small immature MKs undergoing a massive lysis, presumably originating from either FLI1(+) or FL...Continue Reading

References

Jan 1, 1993·Molecular and Cellular Biology·V LemarchandelP H Roméo
Apr 16, 1998·Science·G A HolländerS J Burakoff
Sep 5, 1998·Immunity·I RivièreD R Littman
Sep 10, 1998·Genes & Development·S NewlandsE C Hardeman
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·D L CookS J Tapscott
Apr 7, 1999·Nature Genetics·S L NuttM Busslinger
Mar 23, 2001·Nature Immunology·H Veiga-FernandesB Rocha
Feb 15, 2001·Oncogene·F O BartelD D Spyropoulos
Aug 16, 2001·International Journal of Hematology·Hiroshi KawadaMakio Ogawa
Jan 11, 2002·The New England Journal of Medicine·Eileen M ShoreFrederick S Kaplan
Aug 17, 2002·Science·Michael B ElowitzPeter S Swain
Oct 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ralf KemkemerDieter Kaufmann
Apr 1, 2003·Nature Immunology·João Pedro PereiraPaulo Vieira
Jun 6, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiaobing YuLinzhao Cheng
Nov 5, 2003·Thrombosis and Haemostasis·Remi FavierElisabeth M Cramer
Dec 16, 2003·Molecular and Cellular Biology·Jun LuKatya Ravid

❮ Previous
Next ❯

Citations

Jun 15, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Catherine L Carmichael, Warren S Alexander
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth A KruseBenjamin T Kile
May 28, 2009·Molecular and Cellular Biology·Hui HuangAlan B Cantor
Jul 3, 2004·The Journal of Clinical Investigation·Ramesh A Shivdasani
Dec 3, 2005·The Journal of Clinical Investigation·Liyan PangMortimer Poncz
Aug 25, 2007·The Journal of Clinical Investigation·Konstantin Levay, Vladlen Z Slepak
Sep 29, 2005·Hematology·H SaitoS Kunishima
Sep 1, 2007·Platelets·Caroline PendariesJennifer C Spalton
Jun 13, 2015·Thrombosis and Haemostasis·Darin SiripinSurapol Issaragrisil
May 11, 2016·Platelets·Carlo L BalduiniAlessandro Pecci
Mar 30, 2016·Journal of Applied Genetics·Elisa TassanoCristina Cuoco
Jul 28, 2016·Platelets·Natthapol Songdej, A Koneti Rao
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·L BénitR Favier
Aug 1, 2007·Journal of Thrombosis and Haemostasis : JTH·Y ChangW Vainchenker
Sep 1, 2007·European Journal of Medical Genetics·M ValdugaP Jonveaux
Feb 18, 2017·American Journal of Medical Genetics. Part a·Paul Grossfeld
Jan 19, 2006·American Journal of Medical Genetics. Part a·D BöhmS K Bohlander
Jun 6, 2009·Journal of Cellular Biochemistry·Hui Huang, Alan B Cantor
Mar 1, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Robert D BellJoseph M Miano
Sep 19, 2007·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Hasan Khatib
May 27, 2010·Pediatrics International : Official Journal of the Japan Pediatric Society·Zuhre KayaCandan Ozogul
Feb 28, 2006·American Journal of Medical Genetics. Part a·Sharon L WengerMarybeth Hummel
May 9, 2015·Clinical Genetics·A Savoia
Oct 16, 2007·Oncogene·A N Goldfarb
May 3, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Leila J NoetzliKellie R Machlus
Aug 14, 2012·Human Genetics·Carlo L Balduini, Anna Savoia
Aug 4, 2011·Journal of Thrombosis and Haemostasis : JTH·A Nurden, P Nurden
Aug 2, 2011·Expert Review of Hematology·Kelly CoxWalter H A Kahr
Mar 1, 2012·Journal of Thrombosis and Haemostasis : JTH·V MericoA Balduini
Feb 1, 2014·British Journal of Haematology·Alessandro Pecci, Carlo L Balduini
Jul 1, 2017·Blood·Hervé Falet
Oct 9, 2013·Blood·Jacqueline StockleyUNKNOWN UK Genotyping and Phenotyping of Platelets Study Group

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
FACS
PCR

Software Mentioned

Adobe Photoshop

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Aphasia

Aphasia affects the ability to process language, including formulation and comprehension of language and speech, as well as the ability to read or write. Here is the latest research on aphasia.