Journal
HEMATOLOGY
Volume 26, Issue 1, Pages 88-95Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/16078454.2020.1870373
Keywords
myelodysplastic syndrome; secondary hemochromatosis; reactive oxygen species; dichlorofluorescein; serum ferritin; iron overload; iron chelation therapy; early hematopoietic cells
Categories
Funding
- Leukemia & Lymphoma Society of Canada
- Novartis Pharmaceuticals Canada
- Ontario Student Opportunity Trust Funds Award
- Canadian Blood Services Graduate Fellowship
- estate of J. Douglas Crashley
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By measuring siROS levels in early hematopoietic cells of MDS patients, it was found that high blast MDS patients had lower siROS levels in their BM CD34+ cells, and a narrower siROS distribution, associated with increased reliance on glycolysis and ROS defense. There was a strong correlation between siROS levels in CD34+ cells and serum ferritin levels.
Objectives: Reactive oxygen species (ROS) are under scrutiny as a participant in the pathophysiology of myelodysplastic syndrome (MDS) and the progression of MDS to acute myeloid leukemia (AML). Measurement of intracellular ROS (iROS) is particularly important since iROS is a direct indicator of cellular health and integrity. Methods: We developed a technique to measure standardize iROS (siROS) level in lymphocytes and bone marrow (BM) CD34(+) hematopoietic progenitors using the fluorescent probe dichlorofluorescein (DCF). We then quantified the siROS in 38 consecutive BM specimens from 27 MDS patients over the course of 10 months. Disease outcome of these patients were also assessed. Results: High serum ferritin, high blast count and poor IPSS were associated with inferior survival and AML progression in this cohort. High blast MDS patients had lower siROS in their BM CD34+ cells than those of low blast patients, consistent with increased reliance on glycolysis and enhanced ROS defense in high blast MDS. We also observed narrower siROS distribution in the BM CD34+ cells of high blast patients, suggesting that loss of heterogeneity in ROS content accompanies the clonal evolution of MDS. Furthermore, we observed a strong correlation between CD34+ cells siROS and serum ferritin level in high blast patients. In one case, iron chelation therapy (ICT) resulted in parallel decreases in serum ferritin and CD34(+) cells siROS. Conclusion: Our findings established the siROS profile in early hematopoietic cells of MDS patients and its relationship with blast count and iron overload.
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