Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026986 (
myelodysplastic syndrome
)
14,926
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Bone marrow niche constituents have been implicated in the genesis of clonal hematopoietic dysfunction in
myelodysplastic syndromes
(
MDS
), though the exact role of stroma in the pathogenesis of
MDS
remains to be defined. We have evaluated the characteristics of mesenchymal stromal cells in a cohort of patients with
MDS
with multilineage dysplasia (MDS-MLD). MSCs were cultured from bone marrow aspirates of
MDS
-MLD patients and controls with healthy bone marrow. Phenotypic characterization, cell cycle, and apoptosis were analyzed by flow cytometry. Targeted gene expression analysis was done using a reverse-transcription polymerase chain reaction (Q-PCR). MSCs derived from
MDS
patients (MDS-MSCs) showed normal morphology, phenotype, karyotype and differentiation potential towards adipogenic and osteogenic lineages. However, these
MDS
-MSCs showed significantly altered cell cycle status and displayed a shift towards increased apoptosis compared to control MSCs (C-MSCs). The gene expression profile of niche responsive/regulatory cytokines showed a trend towards lower expression
VEGF
,
SCF
, and
ANGPT
with no changes in expression of
CXCL12A
and
LIF
compared to C-MSCs. The expression levels of Notch signaling components like Notch ligands (
JAGGED
-
1
and
DELTA
-
LIKE
-
1
), receptors (
NOTCH1
,
NOTCH3
) and downstream gene (
HES1
) showed an aberrant expression pattern in
MDS
-MSCs compared to C-MSCs. Similarly, Q-PCR analysis of Wnt signaling inhibitory ligands (
DKK
-
1 and DKK
-
2
) in
MDS
-MSCs showed a three-fold increase in mRNA expression of
DKK1
and a two-fold increase in
DKK2
compared to C-MSCs. These data suggested that
MDS
-MSCs have an altered proliferation characteristic as well as a dysregulated cytokine secretion and signaling profile. These changes could contribute to the pathogenesis of
MDS
.
...
PMID:Heterogeneity of Mesenchymal Stromal Cells in Myelodysplastic Syndrome-with Multilineage Dysplasia (MDS-MLD). 3098 56
