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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.

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

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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