Arsenic Primes Human Bone Marrow CD34+ Cells for Erythroid Differentiation

Abstract

Arsenic trioxide exhibits therapeutic effects on certain blood malignancies, at least partly by modulating cell differentiation. Previous in vitro studies 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.

Hematotoxicity of intratracheally instilled arsenic trioxide in rats

“…The RDW showed little change among the different groups. The first among the possible reasons for these findings is that the total amount of arsenic entering the body by respiration was limited [15]; second, the differentiation of RBCs in the bone marrow hematopoietic system fully compensated for the effects of the arsenic; third, arsenic induced eryptosis was characterized by cell shrinkage [16]; and lastly, the effects on differentiation of bone marrow erythrocytes had not yet appeared [17]. In contrast to the results reported by Luo et al [18], RDW was significantly decreased in the HD group at 12 h. It is likely that because arsenic and phosphorus are of the same group and have the same valence state, they have a competitive relationship in metabolism and that arsenic thus directly inhibits ATPase activity on the erythrocyte membrane, affecting glucose metabolism, and then affecting the morphology of RBCs [19,20].…”

Serum trace metal association with response to erythropoiesis stimulating agents in incident and prevalent hemodialysis patients

“…In studies using CD34 + cells isolated from chronic myeloid leukemia patient bone marrow, sub-toxic levels of arsenic trioxide enhanced or primed erythroid colony forming activity. Additionally the same study demonstrated sub-toxic levels of arsenic trioxide inhibited globin gene expression in K562 cells, a chronic myelogenous leukemia patient derived erythroid-myeloid precursor cell line 53 . While the effect of arsenic appears biphasic in cell culture this cannot be assumed to be the case in the setting of chronic hemodialysis.…”

Toxic effect of copper-zinc pyrite ore on erythropoiesis in chronic experiment

“…Изменения в крови появляются уже при действии сравнительно малых доз токсических веществ [1] и зачастую являются единственным показателем возникающего заболевания или начала развития осложнений [2]. Сам факт влияния отдельных тяжелых металлов на систему крови описан в литературе [3,4], однако сведения об ответных реакциях гемопоэтической ткани при сочетанной интоксикации противоречивы и недостаточны для четкого определения общих медико-экологических закономерностей токсического влияния природных соединений на организм. Изучение патогенеза металлиндуцированных анемий и поиск возможных путей их коррекции -актуальные задачи для медицинской науки Башкортостана, который занимает второе место в Уральском регионе по промышленному потенциалу и является крупнейшим индустриальным центром России.…”