Occurrence of Haemoglobin H in Leukaemia: a Further Case of Erythroleukaemia

Beaven, G. H.; Coleman, P. N.; White, Jay D.

doi:10.1159/000207743

Cited by 7 publications

(1 citation statement)

References 11 publications

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“…Some patients were originally described as having underlying marrow disorders such as diGuglielmo syndrome, atypical erythroid hyperplasia, or erythroleukemia 29,30,34,[36][37][38] 65 In some published reports, such as an instance of atypical chronic myeloid leukemia with HbH disease described in 1963 (only 3 years after the discovery of the Philadelphia chromosome and several years before the advent of routine karyotyping), MDS is a strong possibility, but there is not enough information to make a conclusive retrospective diagnosis. 32 In several other cases that have come to our attention, the quality of archival material has been insufficient to allow a diagnosis more specific than chronic myeloid disorder.…”

Section: ␣-Thalassemia In the Context Of Hematologic Malignancymentioning

confidence: 99%

Acquired α-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies

Steensma

Gibbons

Higgs

2005

Blood

104

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Abnormalities of hemoglobin synthesis are usually inherited but may also arise as a secondary manifestation of another disease, most commonly hematologic neoplasia. Acquired hemoglobin disorders can be seen in any population and are not restricted to areas of the world with high incidences of inherited hemoglobinopathies. In fact, the acquired hemoglobinopathies may be more readily recognized where inherited hemoglobin abnormalities are rare and less likely to cause diagnostic confusion. Acquired ␣-thalassemia is the best characterized of the acquired red blood cell disorders in patients with hematologic malignancy, and it is almost always associated with a myelodysplastic syndrome (MDS). At least 2 molecular mechanisms for acquired ␣-thalassemia are now recognized: acquired deletion of the ␣-globin gene cluster limited to the neoplastic clone and, more commonly, inactivating somatic mutations of the trans-acting chromatin-associated factor ATRX, which cause dramatic downregulation of ␣-globin gene expression. Here we review the clinical, hematologic, and molecular genetic features of ␣-thalassemia arising in a clonal myeloid disorder, and we discuss how ATRX might affect gene expression in normal and abnormal hematopoiesis through epigenetic mechanisms. IntroductionFor more than 4 decades, the synthesis of hemoglobin during erythropoiesis has served as an excellent model for understanding mammalian gene regulation. A diverse repertoire of naturally occurring mutations of the globin genes has enabled researchers to use this system to establish many of the general principles underlying human molecular genetics and, in particular, to advance our understanding of molecular hematology. 1 Although nearly all globin mutations characterized to date have been cis-acting defects, it has recently emerged that globin synthesis may also be altered by trans-acting mutations involving erythroid-specific and general transcriptional regulators. [2][3][4] It has long been recognized that patients with hematologic malignancy and abnormal erythropoiesis may also acquire changes in hemoglobin structure or synthesis, but the molecular basis of such abnormalities remained obscure. However, recent studies of patients with myelodysplasia who acquire thalassemia have identified somatic mutations in a known trans-acting regulator of globin gene expression, ATRX (␣-thalassemia mental retardation X-linked, named after the phenotype associated with germline mutations in the gene). 5,6 Although these new observations will undoubtedly increase our understanding of how globin gene expression is normally controlled, they may also point to common genetic or epigenetic mutations that contribute to the development or progression of myelodysplasia. Normal structure and expression of globin gene clustersThe synthesis of hemoglobin is controlled by 2 developmentally regulated multigene clusters: the ␣-like globin cluster on chromosome 16 (5Ј--␣2-␣1-3Ј) and the ␤-like globin cluster on chromosome 11 (5Ј-⑀-G␥-A␥-␦-␤-3Ј) ( Figure 1). Coordinated expres...

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Section: ␣-Thalassemia In the Context Of Hematologic Malignancymentioning

confidence: 99%

Acquired α-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies

Steensma

Gibbons

Higgs

2005

Blood

104

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Erythroleukemia: A study of 15 cases and literature review

Roggli

Saleem

1982

Cancer

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Out of a total of 185 cases of acute leukemia at our institution from 1967 to 1978, fifteen cases (8.1%) were identified as erythroleukemia or erythremic myelosis. The symptoms at presentation were often related to anemia (10/15 cases); the presenting hemoglobin value was lower than 10.0 gm/100 ml. Nucleated red cells were present in the peripheral blood and reticulocyte response was inappropriate to the degree of anemia. Marrow biopsy showed erythroid hyperplasia with megaloblastic and dyserythropoietic features, increase in myeloblasts greater than 5% (10/15 cases), positive PAS staining of erythroid precursors (12/12 cases), and erythrophagocytosis by abnormal erythroid precursors (6/15 cases). Abnormalities were noted in monocytic and megakaryocytic cell lines, and it was concluded that erythroleukemia is probably a stem cell disorder. Response to chemotherapy was poor with median survival of four months from initial diagnosis. Intracranial hemorrhage and bacterial or fungal infection were the most frequent cause of death.

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2001

The Thalassaemia Syndromes

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Occurrence of Haemoglobin H in Leukaemia: a Further Case of Erythroleukaemia

Cited by 7 publications

References 11 publications

Acquired α-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies

Acquired α-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies

Erythroleukemia: A study of 15 cases and literature review

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