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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.

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

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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