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1/10. The morphology of dyserythropoiesis in a patient with acute erythroleukaemia associated with multiple myeloma.

    A patient with multiple myeloma in whom acute erythroleukaemia developed 5 years following treatment with irradiation and melphalan is reported. Immunoglobulin synthesis and immunofluorescence investigations provided evidence that the blast cells in the peripheral blood did not belong to the plasma cell series; ultrastructure examination demonstrated their myeloid origin. Chromosomally abnormal cells were observed in both the bone marrow and peripheral blood. light-and electron microscopy of erythropoiesis in this case showed distinct features of dyserythropoiesis, similar to those described in other entities. The erythroid cell abnormalities are discussed in the light of their being either indications of malignancy or of a reactive process.
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2/10. Multiple vacuoles formation in erythroblasts in an erythroleukaemic patient.

    Peculiar erythroblasts with multiple vacuoles were observed in the bone marrow of an erythroleukaemic patient. Some erythroblasts contained more than 80 vacuoles on a thin section. The contents of vacuoles were amorphous with low electron density. No transitional form from mitochondria or other organelles was observed. Since these vacuolated erythroblasts were clearly distinguishable from megaloblastoid erythraemia cells, multiple vacuoles formation is presumably attributable to the disturbance of microconnection net work in the normal red cell series.
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3/10. Erythroleukemia in a child associated with monosomy 7.

    A case of erythroleukemia (EL) associated with monosomy 7 is reported. The EL was diagnosed 20 months after the initial diagnosis of monosomy 7 was made. An immunologic study of the blast cells using a monoclonal antibody was positive for glycophorin A, which suggested that they were of erythroid origin; this was confirmed by electron microscopy. Chemotherapy was started with low dose cytarabine. However, the patient had severe bone marrow suppression and died of pneumonia. Our case shows that monosomy 7 is an abnormality of the pluripotential stem cells, including erythroid cells, that resulted in a true erythroid neoplasm.
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4/10. Erythroleukemia in a child: value of immunocytochemistry and transmission electron microscopy in its diagnosis.

    A 4 1/2-year-old girl presented with erythroleukemia (EL) that mimicked acute lymphocytic leukemia (ALL). The diagnosis was established with transmission electron microscopy (TEM) and immunocytochemical staining for hemoglobin. Erythroleukemia may present in childhood and may require TEM and immunocytochemistry to make the diagnosis. The correct diagnosis is extremely important since EL has a much poorer prognosis and requires entirely different therapy. Therefore, it is most important to consider EL in those cases of ALL in which the data are not clear-cut and in which the patient fails to respond.
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5/10. Identification of circulating micromegakaryocytes in a case of erythroleukemia.

    A 26-year-old man with erythroleukemia was found to have circulating micromegakaryocytes . Megakaryocytic features were defined by morphologic and cytochemical studies using light and electron microscopy with platelet-megakaryocyte peroxidase staining. This appears to be the first reported instance of erythroleukemia with circulating micromegakaryocytes .
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6/10. Erythroleukemic infiltration of a lymph node: use of hemoglobin immunohistochemical techniques in diagnosis.

    Isolated submandibular adenopathy developed in a patient who had subacute erythroleukemia. lymph node biopsy revealed a proliferation of immature cells and scattered foci of dyserythropoietic normoblasts. Since a review of the literature revealed no detailed description of an erythroleukemic lymph node infiltrate, a histopathologic study of this node was undertaken. The immature cells were identified as erythroblasts and pronormoblasts by histochemical staining (periodic acid-Schiff reagent and chloroacetate esterase), immunohistochemical reaction (directed against hemoglobin), and electron microscopy. The diagnosis of erythroleukemic lymph node infiltrate may be missed in the absence of a high index of suspicion. It is concluded that the detection of hemoglobin within malignant cells is most helpful in establishing the diagnosis.
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7/10. emperipolesis and annulate lamellae in erythroleukaemia.

    The bone marrow in the erythraemic phase of 2 erythroleukaemia patients was studied electron microscopically. emperipolesis of erythrocytes as well as annulate lamellae were revealed in the cytoplasm of the erythroblasts of these cases. It is assumed that these findings show a high rate of erythroblastic proliferation. This is the first report of emperipolesis within the erythroblast by erythroleukaemia. In addition, other various abnormalities, namely, nuclear-cytoplasmic asynchrony, nuclear bleb or cleft formation, abundant glycogen particles and ferruginous micelles in mitochondria such as described in some previous reports, were also recognized.
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8/10. Ultrastructural and fluorescence microscopy study of a case of acute erythremia.

    The authors studies in fluorescence microscopy and electronic microscopy the dysmorphic erythroblasts of a case of acute erythremia. They found evidence of granular fluorescence on the smears, corresponding to the presence of prophyrins and proteinaceous cristallin structures on the ultrathin sections. It seems to be possible to establish a morphologic correlation between the fluorescent granules and the cristallin structures. Thus, the hypothesis of poryphrins adsorption on cristallin structures may be proposed.
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9/10. The natural history of trilinear myelodysplastic syndrome and erythroleukemia.

    A case of Di Guglielmo's syndrome passed through the three stages of chronic erythromyelosis, erythroleukemia and acute myeloid leukemia (AML). According to the FAB classification the subsequent stages of this syndrome were refractory anemia (RA), RA with excess of blasts (RAEB), AML-M6, AML-M2 and undifferentiated AML-MO as the end-stage disease. light- and electronmicroscopice findings on peripheral blood and bone marrow slides showed a pronounced trilineage myelodysplastic syndrome (MDS) during the RA, RAEB, AML-M6 and M2 phases of the disease, i.e. dysplastic erythropoiesis with PAS-positive erythroblasts, agranular and hypogranular neutrophils and dysplastic megakaryocytes. It is concluded that this case of Di Guglielmo's syndrome with chronic erythromyelosis, erythroleukemia and AML appears to be a continuum of trilineage MDS, AML-M6 and M2 with dyserythropoiesis which evolved into AML-M0.
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10/10. GATA-1 and erythropoietin receptor genes are highly expressed in erythroleukemia.

    We examined expression of the erythroid-associated genes GATA-1 and erythropoietin receptor (EPOR) in primary leukemia using the reverse transcriptase-polymerase chain reaction (RT-PCR). GATA-1 and EPOR mRNAs were detectable in all cases of erythroleukemia (French-American-British classification: M6) or early erythroblastic leukemia. In all other leukemia cases, including M2 through M5, stem cell leukemia, and adult T-cell leukemia, these gene transcripts were undetectable. GATA-2 was detectable in all the cases of primary leukemias examined in this study, except one case of M5. In one case, the phenotype switched from myeloid (M2) to erythroid (M6) and then back to myeloid. Northern blotting and RT-PCR revealed that GATA-1 and EPOR mRNAs were significantly upregulated at the M6 stage compared with the M2 stage. GATA-1 may be involved in the expression of an erythroid phenotype in acute leukemia. We generated HL-60 transfectants exogenously expressing GATA-1. The majority of hl-60 cells expressing GATA-1 lacked azurophilic granules, and electron microscopic analysis revealed that myeloperoxidase activity was negative. Platelet peroxidase activity, which was detectable in both megakaryoblasts and erythroid progenitors, was positive. However, EPOR and glycophorin A mRNAs were undetectable by RT-PCR. These findings suggest that besides GATA-1, a third factor may be required for the expression of mature erythroid phenotypes. In addition, our results indicate that GATA-1 is involved in inactivation of myeloperoxidase and activation of the platelet peroxidase.
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