title: Stem cell origin of myelodysplastic syndromes.
abstract: Myelodysplastic syndromes (MDS) are common hematologic disorders that are characterized by decreased blood counts due to ineffective hematopoiesis. MDS is considered a 'preleukemic' disorder linked to a significantly elevated risk of developing an overt acute leukemia. Cytopenias can be observed in all three myeloid lineages suggesting the involvement of multipotent, immature hematopoietic cells in the pathophysiology of this disease. Recent studies using murine models of MDS as well as primary patient-derived bone marrow samples have provided direct evidence that the most immature, self-renewing hematopoietic stem cells (HSC), as well as lineage-committed progenitor cells, are critically altered in patients with MDS. Besides significant changes in the number and distribution of stem as well as immature progenitor cells, genetic and epigenetic aberrations have been identified, which confer functional changes to these aberrant stem cells, impairing their ability to proliferate and differentiate. Most importantly, aberrant stem cells can persist and further expand after treatment, even upon transient achievement of clinical complete remission, pointing to a critical role of these cells in disease relapse. Ongoing preclinical and clinical studies are particularly focusing on the precise molecular and functional characterization of aberrant MDS stem cells in response to therapy, with the goal to develop stem cell-targeted strategies for therapy and disease monitoring that will allow for achievement of longer-lasting remissions in MDS.
authors: 1] Albert Einstein College of Medicine, Albert Einstein Cancer Center, New York, NY, USA [2] Departments of Cell Biology and Developmental and Molecular Biology, New York, NY, USA [3] Division of Hematologic Malignancies, Department of Medicine (Oncology), New York, NY, USA [4] Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Chanin Institute for Cancer Research, New York, NY, USA.
authors: H K
authors: HK
authors: Elias
authors: 1] Albert Einstein College of Medicine, Albert Einstein Cancer Center, New York, NY, USA [2] Departments of Cell Biology and Developmental and Molecular Biology, New York, NY, USA [3] Division of Hematologic Malignancies, Department of Medicine (Oncology), New York, NY, USA [4] Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Chanin Institute for Cancer Research, New York, NY, USA.
authors: C
authors: C
authors: Schinke
authors: 1] Albert Einstein College of Medicine, Albert Einstein Cancer Center, New York, NY, USA [2] Departments of Cell Biology and Developmental and Molecular Biology, New York, NY, USA [3] Division of Hematologic Malignancies, Department of Medicine (Oncology), New York, NY, USA [4] Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Chanin Institute for Cancer Research, New York, NY, USA.
authors: S
authors: S
authors: Bhattacharyya
authors: 1] Albert Einstein College of Medicine, Albert Einstein Cancer Center, New York, NY, USA [2] Departments of Cell Biology and Developmental and Molecular Biology, New York, NY, USA [3] Division of Hematologic Malignancies, Department of Medicine (Oncology), New York, NY, USA [4] Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Chanin Institute for Cancer Research, New York, NY, USA.
authors: B
authors: B
authors: Will
authors: 1] Albert Einstein College of Medicine, Albert Einstein Cancer Center, New York, NY, USA [2] Departments of Cell Biology and Developmental and Molecular Biology, New York, NY, USA [3] Division of Hematologic Malignancies, Department of Medicine (Oncology), New York, NY, USA [4] Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Chanin Institute for Cancer Research, New York, NY, USA.
authors: A
authors: A
authors: Verma
authors: 1] Albert Einstein College of Medicine, Albert Einstein Cancer Center, New York, NY, USA [2] Departments of Cell Biology and Developmental and Molecular Biology, New York, NY, USA [3] Division of Hematologic Malignancies, Department of Medicine (Oncology), New York, NY, USA [4] Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Chanin Institute for Cancer Research, New York, NY, USA.
authors: U
authors: U
authors: Steidl
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000473:pathology; D051379:Mice; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D013234:Stem Cells / Q000473:pathology*