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LEUKEYOLK SIGNED

Uncovering the origin and mechanisms of Down syndrome-associated leukaemia through human induced pluripotent stem cell-derived haemopoiesis

Total Cost €

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EC-Contrib. €

0

Partnership

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 LEUKEYOLK project word cloud

Explore the words cloud of the LEUKEYOLK project. It provides you a very rough idea of what is the project "LEUKEYOLK" about.

differentiation    malignancy    first    developmental    erythromyeloid    ipsc    independent    sac    perinatal    assays    transient    interrogate    supports    ds    ipscs    derives    yolk    hypothesise    appreciated    generating    paradigmatic    definitive    haemopoiesis    area    ec    differentiating    pluripotent    followed    hscs    myeloid    childhood    therapies    cells    isoform    syndrome    extensive    leukaemogenesis    hsc    leukaemias    embryogenesis    compelling    disease    designing    embryonic    dissecting    contribution    tmd    utero    patients    hyperproliferation    beginning    hypothesis    devoid    shown    mutations    shift    ys    vitro    cancer    landscape    gata1    lastly    recapitulation    nurture    haemopoietic    mechanisms    megakaryocytic    molecular    megakaryoblast    progenitors    primitive    onset    patient    stem    disorder    elucidated    fp7    malignancies    suggests    competitiveness    lineages    cell    leukemias    waves    functional    transcriptional    rarely    vivo    source    origin    least    paradigm    life    broad    emp    myeloproliferative   

Project "LEUKEYOLK" data sheet

The following table provides information about the project.

Coordinator		 OSPEDALE SAN RAFFAELE SRL 

Organization address
address: VIA OLGETTINA 60
city: MILANO
postcode: 20132
website: www.hsr.it

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.
 Coordinator Country Italy [IT]
 Total cost 168˙277 €
 EC max contribution 168˙277 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-SE
 Starting year 2019
 Duration (year-month-day) from 2019-02-01   to  2021-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    OSPEDALE SAN RAFFAELE SRL IT (MILANO) coordinator 168˙277.00

Map

 Project objective

This project aims at dissecting the contribution of yolk sac (YS)-derived haemopoietic progenitors to childhood leukaemias, whose early onset suggests an embryonic origin. Using induced pluripotent stem cell (iPSC) differentiation, we will determine the origin of the Down syndrome-associated transient myeloproliferative disease (DS-TMD), paradigmatic example of perinatal malignancy. TMD, due to megakaryoblast hyperproliferation, has an in utero origin. This supports the compelling hypothesis of a haemopoietic stem cell (HSC)-independent origin of DS-TMD, as during embryogenesis there are at least 3 waves of progenitors with megakaryocytic potential. A first primitive program, followed by the erythromyeloid progenitors (EMP), both YS-derived and devoid of HSC potential; lastly a definitive program, generating HSCs and all haemopoietic lineages. By differentiating iPSCs from a DS-TMD patient through recapitulation of embryonic development, we will interrogate the contribution of primitive, EMP and definitive haemopoiesis to DS-TMD with in vitro/in vivo functional assays. Moreover, we will investigate the molecular mechanisms triggering the disease. As mutations leading to a short GATA1 isoform occur in all cases of DS-TMD, we will analyse how this affects the transcriptional landscape of the cells relevant to the disease. We hypothesise that DS-TMD derives from a rarely appreciated developmental program (the EMP), whose life-long contribution is only beginning to be elucidated. Determining the developmental source and mechanisms of this disorder could help designing new therapies for myeloid malignancies in non-DS patients and could lead to a paradigm shift in the field of haemopoiesis and leukaemogenesis. Research on cancer and childhood leukemias is of broad interest for the EC, as shown by the extensive funding of projects on this topic within the FP7. Our project will further nurture this research area, contributing to increasing European research competitiveness.

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