BACKGROUND: Sideroblastic anemia represents a heterogeneous group of inherited or acquired diseases with disrupted erythroblast iron utilization, ineffective erythropoiesis, and variable systemic iron overload. In a cohort of 421 patients with multisystem mitochondrial diseases, refractory anemia was found in 8 children. RESULTS: Five children had sideroblastic anemia with increased numbers of ring sideroblasts >15%. Two of the children had a fatal course of MLASA1 syndrome (mitochondrial myopathy, lactic acidosis, and sideroblastic anemia [SA]) due to a homozygous, 6-kb deletion in the PUS1 gene, part of the six-member family of pseudouridine synthases (pseudouridylases). Large homozygous deletions represent a novel cause of presumed PUS1-loss-of-function phenotype. The other three children with SA had Pearson syndrome (PS) due to mtDNA deletions of 4 to 8 kb; two of these children showed early onset of PS and died due to repeated sepsis; the other child had later onset of PS and survived as the hematological parameters normalized and the disease transitioned to Kearns-Sayre syndrome. In addition, anemia without ring sideroblasts was found in three other patients with mitochondrial disorders, including two children with later onset of PS and one child with failure to thrive, microcephaly, developmental delay, hypertrophic cardiomyopathy, and renal tubular acidosis due to the heterozygous mutations c.610A>G (p.Asn204Asp) and c.674C>T (p.Pro225Leu) in the COX10 gene encoding the cytochrome c oxidase assembly factor. CONCLUSIONS: Sideroblastic anemia was found in fewer than 1.2% of patients with multisystem mitochondrial disease, and it was usually associated with an unfavorable prognosis.
- Klíčová slova
- MLASA, Pearson syndrome, mitochondrial disorders, mtDNA, ring sideroblasts, sideroblastic anemia,
- MeSH
- acyl-CoA-dehydrogenasa s dlouhým řetězcem nedostatek genetika metabolismus MeSH
- dítě MeSH
- lidé MeSH
- mitochondriální nemoci * genetika metabolismus patologie MeSH
- nemoci svalů * genetika metabolismus patologie MeSH
- předškolní dítě MeSH
- přetížení železem * genetika metabolismus patologie MeSH
- sideroblastická anemie * genetika metabolismus patologie MeSH
- syndrom MELAS * genetika metabolismus MeSH
- vrozené poruchy metabolismu tuků * genetika metabolismus patologie MeSH
- vrozené syndromy selhání kostní dřeně MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acyl-CoA-dehydrogenasa s dlouhým řetězcem MeSH
Nucleoli were studied in the proliferation as well as maturation granulopoietic compartment in patients suffering from refractory anemia with excess blasts (RAEB) of the myelodysplastic syndrome (MDS) by means of simple cytochemical procedures for the demonstration of nucleolar RNA and silver stained proteins of nucleolus organizer regions. Regardless of the procedure used for the nucleolar visualization, early stages of the granulopoietic compartment and particularly myeloblasts of RAEB patients were characterized by reduction of the nucleolar number expressed by the nucleolar coefficient the values of which resembled those described previously in acute myeloid leukemias. The reduced values of the nucleolar coefficient of these cells in silver stained specimens of RAEB patients were accompanied by a decreased number of clusters of silver stained particles representing interphasic silver stained nucleolus organizer regions (AgNORs). The reduction of these clusters was also described previously in leukemic cells. In addition, the differences in the values of the nucleolar coefficient of granulocytic precursors between specimens stained for RNA and those stained with the silver reaction might reflect changing composition and proportions of nucleolar components in the course of the granulocytic development.
- MeSH
- buněčné jadérko * MeSH
- buňky kostní dřeně cytologie MeSH
- granulocyty cytologie MeSH
- histocytochemie MeSH
- lidé MeSH
- myelodysplastické syndromy patologie MeSH
- refrakterní anemie s nadbytkem blastů patologie MeSH
- sideroblastická anemie patologie MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Active hairy cell leukemia is associated with an increase of RDW (Red Cell Distribution Width) which normalizes after successful therapy with 2-chlorodeoxyadenosine (2-CdA). To clarify this phenomenon, bone marrow films performed before therapy with 2-CdA and after its successful completion were subjected to careful evaluation. Dyserythropoietic changes were present in 5 out of 17 patients before the therapy with 2-CdA. In 2 patients the changes were only slight, characterized by irregularities of the shape of nucleus and nuclear contour, in the remaining 3 patients the changes were marked, represented by nuclear lobulation, karyorrhexis and binuclearity, with the presence of ringed sideroblasts in one of them. After therapy with 2-CdA complete hematologic remission was achieved in 4 patients with disappearance of dyserythropoietic changes and normalization of RDW values. In the last patient with ringed sideroblasts despite complete remission with disappearance of tumoral cells in the bone marrow as demonstrated by immunohistochemical analysis of trephine bone marrow biopsy with monoclonal antibody DBA 44 the condition deteriorated, RDW remained unchanged, the sideroblastic anemia progressed.
- MeSH
- abnormální erytrocyty účinky léků ultrastruktura MeSH
- dospělí MeSH
- erytrocytární znaky účinky léků MeSH
- erytropoéza účinky léků MeSH
- imunologické faktory terapeutické užití MeSH
- indukce remise MeSH
- interferon alfa terapeutické užití MeSH
- kladribin farmakologie terapeutické užití MeSH
- kombinovaná terapie MeSH
- kostní dřeň patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- protinádorové antimetabolity farmakologie terapeutické užití MeSH
- senioři MeSH
- sideroblastická anemie farmakoterapie etiologie patologie MeSH
- splenektomie MeSH
- vlasatobuněčná leukemie krev farmakoterapie patologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- imunologické faktory MeSH
- interferon alfa MeSH
- kladribin MeSH
- protinádorové antimetabolity MeSH
Aplastic anemia, myelodysplastic syndromes (MDS) and chronic myeloproliferative diseases (MPD) are stem cell disorders. There is no clear-cut demarcation of them. Hypoplastic MDS displays features of aplastic anemia and MDS, on the other side mixed myelodysplastic and myeloproliferative syndromes (MDS-MPS) develop. In our collection of 566 MDS patients, features of myelodysplasia as well as myeloproliferation, MDS-MPS, were present in 25 patients (4.4%). Twelve patients had at the time of diagnosis megakaryocytic proliferation and thrombocythemia beside signs of MDS, and seven had myelodysplasia with granulocytic proliferation and leukocytosis. In another six patients, MDS was the first diagnosis and the proliferative phase developed later during the course of the disease. These patients can be characterized as MDS-MPS in evolution. All subjects had a variable degree of anemia. While the level of thrombocythemia has been relatively stable, the number of leukocytes has been progressive, but rarely extended beyond 100 x 10(9)/l. Ring-sideroblasts and myelofibrosis were frequent findings. Two more homogeneous MDS-MPS groups emerged in our analysis: sideroblastic anemia with thrombocythemia and a group fulfilling the criteria of Philadelphia chromosome negative and bcr-abl negative "atypical chronic myeloid leukemia (aCML)'. One patient with thrombocythemia and three with leukocytosis (23%) transformed to acute myeloid leukemia (AML). Men prevailed (12/13) in patients with leukocytosis and MDS-MPS in evolution. Of the 46% MDS-MPS patients with chromosomal aberrations, del(20)(q) is of interest.
- MeSH
- chronická myelomonocytární leukemie klasifikace komplikace genetika patologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- refrakterní anemie s nadbytkem blastů klasifikace komplikace genetika patologie MeSH
- refrakterní anemie klasifikace komplikace genetika patologie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sideroblastická anemie klasifikace komplikace genetika patologie MeSH
- trombocytóza klasifikace komplikace patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Myelodysplastic syndrome (MDS) is frequently associated with monocytosis in the blood and myelomonocytic dysplasia in the bone marrow. In two groups of patients with MDS, all subtypes excluding CMML, the authors demonstrated that monocytosis was present in 15% of the patients in group I according to the haemogram at the time when the diagnosis was established and in 19% in group II where it was required that at least in half the haemograms throughout the course of the disease there were more than 10% monocytes. No difference was found in the prognosis of patients with monocytosis, as compared with patients with monocytopenia as regards the life span and frequency of transformation into AL. The cytogenetic and cultivation findings did not differ either. In some instances, in particular in patients with RA and RAS significant monocytosis was not associated with the expected proliferation of monocytoid cells in bone marrow. The authors assume that proliferation and differentiation of germ cells in the monocytic series is easier than in the granulocytic series and that monocytosis can be considered a manifestation of substituted neutropenia. The work indicates the difficulties associated with the differential diagnosis of RA, RAS and RAEB with monocytosis, MDS with a dominating change of the type of myelomonocytic dysplasia and CMML proper.
