Acquired alteration in the expression of blood groups in a patient with sideroblastic anemia and chronic renal failure

Mn, Levine; Wk, Kuhns; Ta, Bolk; Ta, Beyer; Rosse, WF

doi:10.1046/j.1537-2995.1984.24184122568.x

Cited by 11 publications

(2 citation statements)

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“…19 Other examples of acquired red blood cell abnormalities associated with MDS include loss of glycosylphosphatidylinositol (GPI)-anchored proteins including CD55 and CD59, 20 enzymopathies (especially pyruvate kinase deficiency), 21 membrane defects including elliptocytosis, 22 and blood group isotype changes including exposure of cryptantigens. 23,24 To our knowledge this is the first report of a patient with ATMDS in whom an acquired ␣-globin deletion was demonstrable. This case illustrates that the loss of a single ␣-globin cluster can cause a dramatic acquired thalassemic phenotype in MDS.…”

Section: Org Frommentioning

confidence: 76%

Deletion of the α-globin gene cluster as a cause of acquired α-thalassemia in myelodysplastic syndrome

Steensma

Viprakasit

Hendrick

et al. 2004

Blood

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IntroductionThe myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow disorders characterized by ineffective clonal hematopoiesis, acquired genomic instability, and variable risk for transformation to acute leukemia. 1 Most patients with MDS have macrocytic or normocytic anemia, but occasional patients have microcytic red blood cell indices. 2 Rarely, MDS patients with striking hypochromia, microcytosis, and anisopoikilocytosis are found to have acquired hemoglobin H (HbH) disease (␣-thalassemia); this constellation of findings has been called ␣-thalassemia myelodysplastic syndrome (ATMDS). 3 In most patients with ATMDS, a substantial proportion of red blood cells contain HbH inclusions after supravital staining, and severely decreased ␣-globin chain synthesis is paralleled by diminished ␣-globin cytoplasmic and nuclear mRNA levels. 3,4 The common inherited forms of ␣-thalassemia are frequently a consequence of deletions or point mutations affecting the duplicated ␣-globin genes (␣␣/␣␣) on chromosome 16 or, less commonly, deletions of the remote regulatory elements that control ␣-globin expression. 5,6 Germline mutations of ATRX, an X-linked gene encoding a chromatin remodeling protein that regulates the expression of diverse genes, cause mild ␣-thalassemia associated with developmental abnormalities (ATR-X syndrome). 7 ATRX mutations down-regulate the expression of all 4 ␣-globin genes, but the ␣-globin cluster itself is normal.Recently, we have shown that acquired, somatic mutations in the ATRX gene can also underlie ATMDS syndrome. 8,9 To date, 12 unique pathologic ATRX mutations have been found in patients with typical features of ATMDS, including striking "thalassemic" blood pictures, substantial amounts (more than 10%) of HbH, and severely reduced ␣/␤ globin chain biosynthesis ratios. 8,9 However, we have also studied several patients with MDS who have hypochromic, microcytic, red blood cell morphology, but in whom HbH inclusions are only present in a small proportion of erythrocytes or cannot be detected at all. To date, none of these patients have been shown to have mutations in the ATRX gene; the underlying molecular defect remains unknown.Here we report acquired ␣-thalassemia and rare HbH inclusions in an MDS patient. In contrast to previously reported cases of ATMDS, an abnormal hematopoietic clone in this patient had an acquired deletion involving the telomeric region of one allele of chromosome 16, removing 2 of the 4 ␣-genes (ie, genotype ϪϪ/␣␣). This case illustrates a second, less severe mechanism by which ␣-thalassemia may occur as an acquired abnormality in the context of hematologic malignancy. Study designA 72-year-old white British man had microcytic, hypochromic anemia (hemoglobin count, 10.4 g/dL; mean corpuscular volume, 64 fL; mean corpuscular hemoglobin level, 21.7 pg) and neutropenia (leukocyte count, 4.8 ϫ 10 9 /L with 14.7% neutrophils). Two years earlier, he had undergone partial pneumonectomy for localized lung carcinoma; at that time complete blood count finding...

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Section: Org Frommentioning

confidence: 76%

Deletion of the α-globin gene cluster as a cause of acquired α-thalassemia in myelodysplastic syndrome

Steensma

Viprakasit

Hendrick

et al. 2004

Blood

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“…There may be a variety of metabolic abnormalities (Valentine et al, 1973;Cetto et al, 1982), the reappearance of haemoglobin F (Richard et al, 1979), acquired haemoglobin H (Boehme et al, 1978) and changes in membrane antigens (Levine et al, 1984). These changes are associated with gross dyserythropoietic appearances in the bone marrow with both nuclear and cytoplasmic abnormalities.…”

Section: Clinical Datamentioning

confidence: 99%

Human preleukaemia: do we have a model?

Jacobs¹

1987

Br J Cancer

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Myelodysplastic Syndromes

Dusek¹,

Bednár²,

Dorazilová³

et al. 2018

Hematologic Malignancies

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FAS gene, a direct target for NFκB transcription factor, is repressed in solid tumors including colon carcinomas. We have previously reported that, while overexpressed in low risk myelodysplastic syndromes (MDS), the Fas death receptor becomes undetectable on CD34 + progenitors when the disease progresses to secondary acute myeloid leukaemia (sAML). This study aimed at investigating the interplay between NFκB and Fas during MDS progression.We first observed that Fas was inducible by TNFα in the HL60 cell line. In these cells, p65/RelA bound to the chromatin at FAS promoter, while inhibition of NFκB pathway by IKKα inhibitor BAY11-7082 or lentiviral expression of a non-degradable mutant of IκBα, IκSR blocked the expression of Fas. By contrast, TNFα failed to induce Fas expression in the colon carcinoma cell line SW480, due to hypermethylation of the FAS promoter. In vitro use of azacitidine rescued p65/RelA binding on FAS promoter and, subsequently Fas expression in SW480 cells. We also show that, inhibition of NFκB pathway decreased the expression of Fas in MDS CD45 lo CD34 + bone marrow cells. However, despite of the nuclear expression of p65/RelA, Fas was often low on CD45 lo CD34 + AML cells. TNFα failed to stimulate its expression, while azacitidine efficiently rescued p65/RelA binding and Fas reexpression. Our data suggest that DNA methylation at NFκB sites is responsible for FAS gene silencing. Rescuing FAS gene expression by azacitidine could contribute to slacken the progression to leukaemia.

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Acquired alteration in the expression of blood groups in a patient with sideroblastic anemia and chronic renal failure

Cited by 11 publications

References 0 publications

Deletion of the α-globin gene cluster as a cause of acquired α-thalassemia in myelodysplastic syndrome

Deletion of the α-globin gene cluster as a cause of acquired α-thalassemia in myelodysplastic syndrome

Human preleukaemia: do we have a model?

Myelodysplastic Syndromes

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