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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.

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

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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The information about "LEUKEYOLK" are provided by the European Opendata Portal: CORDIS opendata.

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