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Increased apoptosis in acquired sideroblastic anaemia
Author(s) -
Matthes Thomas W.,
Meyer Geneviève,
Samii Kaveh,
Beris Photis
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2000.02425.x
Subject(s) - sideroblastic anemia , ineffective erythropoiesis , bone marrow , apoptosis , biology , erythropoiesis , mitochondrion , annexin , immunology , microbiology and biotechnology , anemia , endocrinology , medicine , biochemistry
Idiopathic acquired sideroblastic anaemias (IASAs) form a subgroup of the myelodysplastic syndromes and are characterized by mitochondrial iron accumulation, bone marrow erythroid hyperplasia and decreased peripheral red blood cell counts. Increased intramedullary apoptosis of erythroid precursors is presumed to constitute the pathophysiological mechanism explaining this ineffective erythropoiesis, but if and how mitochondrial dysfunction is implicated in this process is currently unknown. We therefore studied bone marrow precursor cells obtained from nine patients with IASA for (i) caspase 3 activity, (ii) numbers of Annexin V‐ and 7‐amino‐actinomycin‐positive cells, (iii) numbers of cells with diminished mitochondrial membrane potential, ΔΨ m , and (iv) numbers of cells producing reactive oxygen species (ROS), and we compared the results with those of five normal bone marrow samples. Compared with controls, we found increased caspase 3 activity in all IASA samples, which correlated with increased numbers of Annexin‐V‐positive cells ( r = 0·7). Analysis of different subpopulations showed increased apoptosis in erythroid populations compared with myeloid and/or lymphoid populations in five out of nine cases, and increased apoptosis in the last two populations in four out of nine cases. As evidence of mitochondrial dysfunction, ΔΨ m was found to be diminished in the erythroid subpopulations of all cases of IASA (66·6 ± 17% vs. 34·6 ± 12% in normals). ΔΨ m decrease was correlated to Annexin V positivity ( r = 0·7). Astonishingly, no difference was found between IASA and normal bone marrows with regard to the number of ROS‐producing cells. In fact, both groups exhibited a similar low proportion of ROS production (10·3 ± 7% in normals vs. 6·8 ± 5% in IASA). Taken together, our results show that mitochondria are clearly implicated in the apoptotic process in IASA patients. Whether this is a result of an intramitochondrial defect (e.g. Fe accumulation, secondary to mitochondrial or nuclear DNA mutations) or is secondary to an extracellular stimulus [e.g. tumour necrosis factor (TNF), Fas ligand (FasL)] remains to be determined.