Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia
Copyright policy )Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia
RNA-binding proteins of the Musashi (Msi) family are expressed in stem cell compartments and in aggressive tumors, but they have not yet been widely explored in the blood. Here we demonstrate that Msi2 is the predominant form expressed in hematopoietic stem cells (HSCs), and its knockdown leads to reduced engraftment and depletion of HSCs in vivo. Overexpression of human MSI2 in a mouse model increases HSC cell cycle progression and cooperates with the chronic myeloid leukemia-associated BCR-ABL1 oncoprotein to induce an aggressive leukemia. MSI2 is overexpressed in human myeloid leukemia cell lines, and its depletion leads to decreased proliferation and increased apoptosis. Expression levels in human myeloid leukemia directly correlate with decreased survival in patients with the disease, thereby defining MSI2 expression as a new prognostic marker and as a new target for therapy in acute myeloid leukemia (AML).
- Massachusetts Institute of Technology United States
- University of Queensland Australia
- Whitehead Institute for Biomedical Research United States
- Children's Hospital Tunisia
- Harvard University United States
Rna-Binding Protein, Stem-Cells, Gene-Expression, Mice, Transgenic, Models, Biological, Transformation, Oncogenic Pathway Signatures, Mice, Therapeutic-Efficacy, Biomarkers, Tumor, Animals, Humans, Neoplasm Invasiveness, Cells, Cultured, Progression, Gene Expression Regulation, Leukemic, RNA-Binding Proteins, Hematopoietic Stem Cells, Prognosis, Hematopoiesis, Up-Regulation, Leukemia, Myeloid, Acute, Cell Transformation, Neoplastic, Human Cancer, Differentiation, Disease Progression, Progenitor
Rna-Binding Protein, Stem-Cells, Gene-Expression, Mice, Transgenic, Models, Biological, Transformation, Oncogenic Pathway Signatures, Mice, Therapeutic-Efficacy, Biomarkers, Tumor, Animals, Humans, Neoplasm Invasiveness, Cells, Cultured, Progression, Gene Expression Regulation, Leukemic, RNA-Binding Proteins, Hematopoietic Stem Cells, Prognosis, Hematopoiesis, Up-Regulation, Leukemia, Myeloid, Acute, Cell Transformation, Neoplastic, Human Cancer, Differentiation, Disease Progression, Progenitor
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