Relationship of HIF1α expression with apoptosis and cell cycle in bone marrow mesenchymal stem cells from patients with myelodysplastic syndrome.
Mol Med Rep
; 26(1)2022 Jul.
Article
en En
| MEDLINE
| ID: mdl-35642674
ABSTRACT
Myelodysplastic syndrome (MDS) is a group of abnormal clonal disorders with ineffective hematopoiesis, which are incurable with conventional therapy. Of note, MDS features an abnormal bone marrow microenvironment, which is related to its incidence. The hypoxiainducible factor1α (HIF1α) transcriptional signature is generally activated in bone marrow stem/progenitor cells of patients with MDS. To analyze the expression of HIF1α in bone marrow mesenchymal stem cells (BMMSCs) and the apoptosis and cell cycle features associated with the disease, BMMSCs were obtained from 40 patients with a definitive diagnosis of MDS and 20 subjects with hemocytopenia but a negative diagnosis of MDS as a control group. Reverse transcriptionquantitative PCR and western blot analyses were used to measure HIF1α expression in cells from the two groups and apoptosis and cell cycle were also analyzed and compared between the groups using flow cytometry assays. BMMSCs from both the control group and the MDS group exhibited a fibroblastlike morphology, had similar growth cycles and were difficult to passage stably. It was observed that BMMSCs from the MDS group had significantly higher HIF1α expression levels than the control group (P<0.05). Furthermore, the BMMSCs from the MDS group had a higher proportion of cells in early apoptosis (5.22±1.34 vs. 2.04±0.08%; P<0.0001) and late apoptosis (3.38±0.43 vs. 1.23±0.11%; P<0.01) and exhibited cell cycle arrest. This may be a noteworthy aspect of the pathogenesis of MDS and may be related to high HIF1α expression under a hypoxic state in the bone marrow microenvironment. Furthermore, the expression of HIF1α in bone marrow tissue sections from patients with MDS in the International Prognostic Scoring System (IPSS) lowerrisk group was higher than that from patients with MDS in the IPSS highrisk group. These results revealed the role of HIF1α as a central pathobiology mediator of MDS and an effective therapeutic target for a broad spectrum of patients with MDS, particularly for patients in the lowerrisk group.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Síndromes Mielodisplásicos
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
/
Células Madre Mesenquimatosas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Año:
2022
Tipo del documento:
Article