Arsenic Primes Human Bone Marrow CD34+ Cells for Erythroid Differentiation
Open Access
- 1 January 2015
- journal article
- Published by Hindawi Limited in Bioinorganic Chemistry and Applications
- Vol. 2015, 1-6
- https://doi.org/10.1155/2015/751013
Abstract
Arsenic trioxide exhibits therapeutic effects on certain blood malignancies, at least partly by modulating cell differentiation. Previousin vitrostudies in human hematopoietic progenitor cells have suggested that arsenic may inhibit erythroid differentiation. However, these effects were all observed in the presence of arsenic compounds, while the concomitant cytostatic and cytotoxic actions of arsenic might mask a prodifferentiating activity. To eliminate the potential impacts of the cytostatic and cytotoxic actions of arsenic, we adopted a novel protocol by pretreating human bone marrow CD34+ cells with a low, noncytotoxic concentration of arsenic trioxide, followed by assaying the colony forming activities in the absence of the arsenic compound. Bone marrow specimens were obtained from chronic myeloid leukemia patients who achieved complete cytogenetic remission. CD34+ cells were isolated by magnetic-activated cell sorting. We discovered that arsenic trioxide enhanced the erythroid colony forming activity, which was accompanied by a decrease in the granulomonocytic differentiation function. Moreover, in erythroleukemic K562 cells, we showed that arsenic trioxide inhibited erythrocyte maturation, suggesting that arsenic might have biphasic effects on erythropoiesis. In conclusion, our data provided the first evidence showing that arsenic trioxide could prime human hematopoietic progenitor cells for enhanced erythroid differentiation.Keywords
Funding Information
- National Basic Research Program of China (2010CB529202, NCET-10-0555)
This publication has 29 references indexed in Scilit:
- Impact of arsenic trioxide in the treatment of acute promyelocytic leukemiaLeukemia, 2011
- From an old remedy to a magic bullet: molecular mechanisms underlying the therapeutic effects of arsenic in fighting leukemiaBlood, 2011
- CD49d blockade by natalizumab in patients with multiple sclerosis affects steady-state hematopoiesis and mobilizes progenitors with a distinct phenotype and functionBone Marrow Transplantation, 2010
- The integrin 9 1 on hematopoietic stem and progenitor cells: involvement in cell adhesion, proliferation and differentiationHaematologica, 2009
- Multilevel targeting of hematopoietic stem cell self-renewal, differentiation and apoptosis for leukemia therapyPharmacology & Therapeutics, 2009
- Differentiation therapy of leukemia: 3 decades of developmentBlood, 2009
- Induction of endogenous γ-globin gene expression with decoy oligonucleotide targeting Oct-1 transcription factor consensus sequenceJournal of Hematology & Oncology, 2009
- TSC–mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen speciesThe Journal of Experimental Medicine, 2008
- Inorganic arsenic induces necrosis of human CD34‐positive haematopoietic stem cellsEnvironmental Toxicology and Water Quality, 2008
- CD34 + and Endothelial Progenitor Cells in Patients With Various Degrees of Congestive Heart FailureCirculation, 2004