Prospective evaluation of the effect of deferasirox on hematologic response in transfusion‐dependent patients with low‐risk <scp>MDS</scp> and iron overload

Rosé, Christian; Lenoir, Caroline; Gyan, Emmanuel; Hacini, Maya; Amé, Shanti; Corront, Bernadette; Beyne‐Rauzy, Odile; Adiko, Didier; Loppinet, Elena; Ali-Ammar, Nadia; Laribi, Kamel; Wattel, Éric; Dreyfus, François; Roué, Claire S; Chèze, Stéphane

doi:10.1111/ejh.13088

Cited by 5 publications

(1 citation statement)

References 36 publications

(71 reference statements)

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“…Excessive iron accumulates in the bone marrow including the hematopoietic cells compartment where it induces the generation of ROS, thereby injuring hematopoietic cells [9,17]. Consistent with these observations, iron chelation therapy is associated with dramatic improvements in erythropoiesis, granulopoiesis and megakaryopoiesis in a significant proportion of patients with hematopoietic diseases [18,19,20]. In addition, transferrin may also function to prevent or reduce iron accumulation in tissues, and this agent, in the form of apotransferrin, is under investigation for its therapeutic potential to prevent disease progression in thalassemia [21].…”

Section: Introductionmentioning

confidence: 96%

Excessive Reactive Iron Impairs Hematopoiesis by Affecting Both Immature Hematopoietic Cells and Stromal Cells

Tanaka

Espinoza

Fujiwara

et al. 2019

Cells

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Iron overload is the accumulation of excess iron in the body that may occur as a result of various genetic disorders or as a consequence of repeated blood transfusions. The surplus iron is then stored in the liver, pancreas, heart and other organs, which may lead to chronic liver disease or cirrhosis, diabetes and heart disease, respectively. In addition, excessive iron may impair hematopoiesis, although the mechanisms of this deleterious effect is not entirely known. In this study, we found that ferrous ammonium sulfate (FeAS), induced growth arrest and apoptosis in immature hematopoietic cells, which was mediated via reactive oxygen species (ROS) activation of p38MAPK and JNK pathways. In in vitro hematopoiesis derived from embryonic stem cells (ES cells), FeAS enhanced the development of dysplastic erythroblasts but inhibited their terminal differentiation; in contrast, it had little effect on the development of granulocytes, megakaryocytes, and B lymphocytes. In addition to its directs effects on hematopoietic cells, iron overload altered the expression of several adhesion molecules on stromal cells and impaired the cytokine production profile of these cells. Therefore, excessive iron would affect whole hematopoiesis by inflicting vicious effects on both immature hematopoietic cells and stromal cells.

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