P060 CD34+ marrow cells from MDS patients are characterized by higher levels of intracellular reactive oxygen species and inadequate antioxidant defences

Voukelatou, Georgia; Thanopoulou, Eleni; Dallas, Kai; Fertakis, V.; Dimopoulou, Aikaterini; Micheva, Ilina; Lampropoulou, P.; Kouraklis-Symeonidis, Alexandra; Symeonidis, Argiris; Zoumbos, Nicholas

doi:10.1016/s0145-2126(09)70140-7

Cited by 2 publications

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“…In this report, we show an increase in ROS can be detected in both the proliferative, CD71+ BMNC as well as the LN BMNC from NHD13 mice. The markedly elevated levels of ROS in LN BMNC from NHD13 mice is consistent with the observation that primitive hematopoietic (CD34+) cells from MDS patients have higher level of intracellular ROS than normal CD34+ cells [20]. …”

Section: Discussionsupporting

confidence: 87%

“…Several studies have demonstrated that markers of oxidative stress, such as elevated levels of ROS and DNA damage, can be detected in MDS patients [17–20]. In this report, we show an increase in ROS can be detected in both the proliferative, CD71+ BMNC as well as the LN BMNC from NHD13 mice.…”

Section: Discussionsupporting

confidence: 63%

“…Furthermore, this genomic instability is predicted to result in mutations of genes that collaborate with the BCR-ABL fusion protein, resulting in the transition from chronic phase to blast crisis [14, 15]. With regard to MDS and oxidative stress, several studies have reported that increased levels of ROS or oxidative DNA damage could be detected in hematopoietic cells from MDS patients [16–20]. …”

Section: Introductionmentioning

confidence: 99%

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Oxidative stress leads to increased mutation frequency in a murine model of myelodysplastic syndrome

et al. 2014

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The myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, dysplasia, and transformation to acute myeloid leukemia (AML). Although it has been suggested that additional mutations lead to progression of MDS to AML, the causative agent(s) for such mutations remains unclear. Oxidative stress is a potential cause, therefore, we evaluated levels of reactive oxygen species (ROS) in NUP98-HOXD13 (NHD13) transgenic mice, a murine model for MDS. Increased levels of ROS were detected in bone marrow nucleated cells (BMNC) that express CD71, a marker for cell proliferation, as well as immature, lineage negative bone marrow nucleated cells from NHD13 mice. In addition to the increase in ROS, increased DNA double strand breaks and activation of a G2/M phase cell cycle checkpoint were noted in NHD13 BMNC. Finally, using an in vivo assay for mutation frequency, we detected an increased mutation frequency in NHD13 BMNC. These results suggest that oxidative stress may contribute to disease progression of MDS to AML through ineffective repair of DNA damage and acquisition of oncogenic mutations.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

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Oxidative stress leads to increased mutation frequency in a murine model of myelodysplastic syndrome

et al. 2014

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Oxidative stress and mitochondrial dysfunction play a role in myelodysplastic syndrome development, diagnosis, and prognosis: A pilot study

Gonçalves

Cortesão

Oliveiros

et al. 2015

Free Radical Research

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The imbalance between reactive oxygen species (ROS) production and their elimination by antioxidants leads to oxidative stress. Depending on their concentration, ROS can trigger apoptosis or stimulate cell proliferation. We hypothesized that oxidative stress and mitochondrial dysfunction may participate not only in apoptosis detected in some myelodysplastic syndrome (MDS) patients, but also in increasing proliferation in other patients. We investigated the involvement of oxidative stress and mitochondrial dysfunction in MDS pathogenesis, as well as assessed their diagnostic and prognostic values. Intracellular peroxides, superoxide, superoxide/peroxides ratio, reduced glutathione (GSH), and mitochondrial membrane potential (Δψ(mit)) levels were analyzed in bone marrow cells from 27 MDS patients and 12 controls, by flow cytometry. We observed that all bone marrow cell types from MDS patients had increased intracellular peroxide levels and decreased GSH content, compared with control cells. Moreover, oxidative stress levels were MDS subtype- and risk group-dependent. Low-risk patients had the highest ROS levels, which can be related with their high apoptosis; and intermediate-2-risk patients had high Δψ(mit) that may be associated with their proliferative potential. GSH levels were negatively correlated with transfusion dependency, and peroxide levels were positively correlated with serum ferritin level. GSH content proved to be an accurate parameter to discriminate patients from controls. Finally, patients with high ROS or low GSH levels, as well as high superoxide/peroxides ratio had lower overall survival. Our results suggest that oxidative stress and mitochondrial dysfunction are involved in MDS development, and that oxidative stress parameters may constitute novel diagnosis and/or prognosis biomarkers for MDS.

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P060 CD34+ marrow cells from MDS patients are characterized by higher levels of intracellular reactive oxygen species and inadequate antioxidant defences

Cited by 2 publications

References 0 publications

Oxidative stress leads to increased mutation frequency in a murine model of myelodysplastic syndrome

Oxidative stress leads to increased mutation frequency in a murine model of myelodysplastic syndrome

Oxidative stress and mitochondrial dysfunction play a role in myelodysplastic syndrome development, diagnosis, and prognosis: A pilot study

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