Stem cell origin of myelodysplastic syndromes

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.Oncogene advance online publication, 16 December 2013; doi:10.1038/onc.2013.520.

Original languageEnglish (US)
JournalOncogene
DOIs
StateAccepted/In press - Dec 16 2013

Fingerprint

Myelodysplastic Syndromes
Stem Cells
Aptitude
Hematopoiesis
Hematopoietic Stem Cells
Oncogenes
Epigenomics
Publications
Leukemia
Therapeutics
Bone Marrow
Recurrence

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Stem cell origin of myelodysplastic syndromes. / Elias, H. K.; Schinke, C.; Bhattacharyya, Sanchari; Will, Britta; Verma, Amit K.; Steidl, Ulrich G.

In: Oncogene, 16.12.2013.

Research output: Contribution to journalArticle

@article{7961b57d85734903b855ac8c7af4f421,
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.Oncogene advance online publication, 16 December 2013; doi:10.1038/onc.2013.520.",
author = "Elias, {H. K.} and C. Schinke and Sanchari Bhattacharyya and Britta Will and Verma, {Amit K.} and Steidl, {Ulrich G.}",
year = "2013",
month = "12",
day = "16",
doi = "10.1038/onc.2013.520",
language = "English (US)",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Stem cell origin of myelodysplastic syndromes

AU - Elias, H. K.

AU - Schinke, C.

AU - Bhattacharyya, Sanchari

AU - Will, Britta

AU - Verma, Amit K.

AU - Steidl, Ulrich G.

PY - 2013/12/16

Y1 - 2013/12/16

N2 - 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.Oncogene advance online publication, 16 December 2013; doi:10.1038/onc.2013.520.

AB - 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.Oncogene advance online publication, 16 December 2013; doi:10.1038/onc.2013.520.

UR - http://www.scopus.com/inward/record.url?scp=84890005056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890005056&partnerID=8YFLogxK

U2 - 10.1038/onc.2013.520

DO - 10.1038/onc.2013.520

M3 - Article

JO - Oncogene

JF - Oncogene

SN - 0950-9232

ER -