ENAGenomicsChildren's clinic 3, University Hospital Essenhttps://www.ebi.ac.uk/ena/browser/view/PRJNA577634Homo sapiensBone marrow fibrosis (BMF) is a rare complication in acute leukemia. In pediatrics, it predominantly occurs in acute megakaryoblastic leukemia (AMKL) and here especially in patients with trisomy 21, called myeloid leukemia in Down syndrome (ML-DS). Defects in mesenchymal stromal cells (MSCs) and cytokines specifically released by the myeloid blasts are the main drivers of fibrosis in the bone marrow niche (BMN). In order to determine which factors are necessary/sufficient for the BMF, we first established MSCs from pediatric patients with AMKL and ML-DS. Healthy donor (HD) control MSCs were established from children and adolescents ≤18 years of age. Steady-state analyses of the MSCs revealed that patient-derived MSCs exhibited decreased adipogenic differentiation potential, enrichment of proliferation-associated genes and upregulation of the oncofetal protein IF2B3. TGFB1 exposure in vitro promoted early profibrotic changes in all three MSC entities. To study BMF induction for longer periods of time, we created an in vivo humanized artificial BMN in immunodeficient mice. Injection of AMKL blasts as producers of TGFB1 specifically induced fibrosis grade I/II in a dose-dependent fashion, thus strongly suggesting TGFB1 excess to be sufficient for BMF. Our in vivo BMF model will be instrumental to specifically prevent the BMF and to identify potentially druggable target genes. We used microarrays to obtain a global overview of the differences between undifferentiated ML-DS- and AMKL-MSC compared to HD-MSC Overall design: Isolated and expanded MSC were cultured until a density of 80-90% followed by RNA extraction and hybridization on Affymetrix microarrays. We performed a gene expression profile of MSC from 8 ML-DS, 5 AMKL patients and 5 HD.ENAMultipotent Bone Marrow Stromal Cells, data, Mesenchymal Stem Cell, Adipose-Derived Mesenchymal Stem Cell, human being, Mrtf-A, Mesenchymal Stem Cells, Modern, Progenitor Cells, Stem Cells, Progenitor Cell, Stromal Cells, AMKL, Mesenchymal Stromal Cells, Adipose Tissue Derived Mesenchymal Stromal Cell, Mesenchymal Progenitor Cells, Wharton's Jelly Cells, Multipotent Mesenchymal Stromal Cell, Adipose Tissue-Derived Mesenchymal Stem Cell, Human, bone marrow stromal cells, stem cells, Mesenchymal Stromal Cell, Client., Homo sapiens, colony-forming unit-fibroblast, Stem Cell, medulla ossium, Stromal Cell, Marrow, medulla ossea, Wharton Jelly Cells, Yellow, mesenchymal precursor cell, Mal, Man, Wharton's Jelly Cell, mesenchymal stromal cell, Multipotent Mesenchymal Stromal Cells, acute myeloblastic leukemia type 7, Adipose Tissue-Derived Mesenchymal Stromal Cells, Bone Marrow Stromal Cell, Yellow Marrow, Adipose-Derived, Adipose Derived Mesenchymal Stem Cells, BMSC, Adipose-Derived Mesenchymal Stem Cells, mesenchymal stromal cells, Man (Taxonomy), Adipose Tissue Derived Mesenchymal Stromal Cells, medullary bone, medulla of bone, Bsac, Multipotent Bone Marrow Stromal Cell, Adipose Tissue-Derived Mesenchymal Stromal Cell, mesenchymal progenitor cells, mesenchymal, Bone Marrow Stromal Stem Cells, Adipose Tissue Derived Mesenchymal Stem Cells, CFU-F, man, MSC, human, Adipose-Derived Mesenchymal Stromal Cells, Red Marrow, Adipose Derived, megakaryocytic leukemia, mesenchymal stem cell, Bone Marrow Mesenchymal Stem Cells, Adipose Tissue-Derived Mesenchymal Stem Cells, Mesenchymal Progenitor Cell, Patient, Whartons Jelly Cells, megakaryocytic leukaemia, Clients, Modern Man, Multipotent, Mesenchymal, Adipose Derived Mesenchymal Stromal Cells, marrow stromal cells, acute myeloblastic leukaemia type 7, Red, Adipose Tissue Derived Mesenchymal Stem Cell, Bone Marrow Stromal Cells, Bone Marrow Mesenchymal Stem Cell, Bone, Adipose Derived Mesenchymal Stem CellMultipotent Bone Marrow Stromal Cells, data, Mesenchymal Stem Cell, Adipose-Derived Mesenchymal Stem Cell, human being, Mrtf-A, Mesenchymal Stem Cells, Modern, Progenitor Cells, Stem Cells, Progenitor Cell, Stromal Cells, AMKL, Mesenchymal Stromal Cells, Adipose Tissue Derived Mesenchymal Stromal Cell, Mesenchymal Progenitor Cells, Wharton's Jelly Cells, Multipotent Mesenchymal Stromal Cell, Adipose Tissue-Derived Mesenchymal Stem Cell, Human, bone marrow stromal cells, stem cells, Mesenchymal Stromal Cell, Client., Homo sapiens, colony-forming unit-fibroblast, Stem Cell, medulla ossium, Stromal Cell, Marrow, medulla ossea, Wharton Jelly Cells, Yellow, mesenchymal precursor cell, Mal, Man, Wharton's Jelly Cell, mesenchymal stromal cell, Multipotent Mesenchymal Stromal Cells, acute myeloblastic leukemia type 7, Adipose Tissue-Derived Mesenchymal Stromal Cells, Bone Marrow Stromal Cell, Yellow Marrow, Adipose-Derived, Adipose Derived Mesenchymal Stem Cells, BMSC, Adipose-Derived Mesenchymal Stem Cells, mesenchymal stromal cells, Man (Taxonomy), Adipose Tissue Derived Mesenchymal Stromal Cells, medullary bone, medulla of bone, Bsac, Multipotent Bone Marrow Stromal Cell, Adipose Tissue-Derived Mesenchymal Stromal Cell, mesenchymal progenitor cells, mesenchymal, Bone Marrow Stromal Stem Cells, Adipose Tissue Derived Mesenchymal Stem Cells, CFU-F, man, MSC, human, Adipose-Derived Mesenchymal Stromal Cells, Red Marrow, Adipose Derived, megakaryocytic leukemia, mesenchymal stem cell, Bone Marrow Mesenchymal Stem Cells, Adipose Tissue-Derived Mesenchymal Stem Cells, Mesenchymal Progenitor Cell, Patient, Whartons Jelly Cells, megakaryocytic leukaemia, Clients, Modern Man, Multipotent, Mesenchymal, Adipose Derived Mesenchymal Stromal Cells, marrow stromal cells, acute myeloblastic leukaemia type 7, Red, Adipose Tissue Derived Mesenchymal Stem Cell, Bone Marrow Stromal Cells, Bone Marrow Mesenchymal Stem Cell, Bone, Adipose Derived Mesenchymal Stem CellfalseExpression data of human mesenchymal stromal cells isolated from bone marrow of ML-DS, AMKL patients and HDExpression data of human mesenchymal stromal cells isolated from bone marrow of ML-DS, AMKL patients and HD2025-09-242020-07-28PRJNA577634GSE1388619606