1/18. Isochromosome (7)(q10) in Shwachman syndrome without MDS/AML and role of chromosome 7 anomalies in myeloproliferative disorders.Shwachman syndrome (SS) is an autosomal recessive disorder in which bone marrow dysfunction is observed, with development of myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML) in up to one third of the cases. Inconclusive data are available as to increased chromosome breakage in SS, while chromosome 7 anomalies, and often an isochromosome (7)(q10), are frequent in cases with MDS/AML. We report on the consistent presence of an i(7)(q10) in the bone marrow and blood lymphocytes in one of two sisters affected with SS without any clinical or cytological signs of MDS/AML. Thus, this patient was either a case of constitutional mosaicism for the i(7)(q10), or this had to be acquired in a nondysplastic and non-neoplastic marrow clone. dna polymorphism analysis demonstrated the paternal origin of the i(7q). We postulate that the SS mutation acts as a mutator gene, and causes karyotype instability; abnormal clones would thus arise in the marrow, and chromosome 7 anomalies, i(7q) in particular, will in turn lead to MDS/AML. If this interpretation is correct, it would be also an indication to consider chromosome 7 anomalies in general, out of SS, as primary changes in MDS/AML pathogenesis.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
2/18. Purine nucleoside phosphorylase deficiency associated with a dysplastic marrow morphology.Purine nucleoside phosphorylase (PNP) deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency and by complex neurologic symptomatology including ataxia, developmental delay, and spasticity. Herein we report severe marrow dysplasia in a patient with PNP deficiency. Drug-related marrow dysfunction was unlikely, and marrow virological studies were negative. A preleukemic myelodysplastic syndrome was also unlikely due to normal marrow CD34 cells, colony growth in clonogenic assay of marrow mononuclear cells, apoptosis rate, and Fas expression on marrow nucleated cells, as well as morphologic improvement of the marrow dysplasia after normal red blood cell transfusion. The patient's marrow stroma showed hypersensitivity to irradiation and undetectable PNP enzyme activity similar to peripheral lymphocytes. This is the first report of PNP deficiency associated with increased lymphocyte and marrow stromal sensitivity to irradiation. We conclude that marrows from patients with PNP deficiency might have hypersensitivity to irradiation and can develop dysplastic morphology, caused either directly or indirectly by the inherited enzymatic defect.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
3/18. ellis-van creveld syndrome and dyserythropoiesis.Ellis-van Creveld (EVC) syndrome or chondroectodermal dysplasia is a rare autosomal recessive disorder characterized by a variable spectrum of clinical findings. Classical EVC syndrome comprises a tetrad of clinical manifestations of chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac defects. In several case reports, dysplasia involving other organs has also been identified. Hematologic abnormalities have been rarely reported in patients with EVC syndrome. Here, we report a case of a 3-year-old Hispanic boy with EVC syndrome and marked dyserythropoiesis. The dyserythropoiesis may be part of an isolated myelodysplastic change or a primary myelodysplastic syndrome and likely represents an unusual EVC syndrome association. To our knowledge, this association has not been previously reported.- - - - - - - - - - ranking = 1.2954737233098keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
4/18. serum transferrin receptor measurements in hematologic malignancies.An enzyme-linked immunosorbent assay using specific monoclonal antibodies was used to measure circulating transferrin receptor (TR) in 87 patients with various hematologic malignancies. The mean serum TR was significantly elevated in patients with myeloproliferative disorders (15.47 /- 12.54 micrograms/ml), whereas there were no differences in chronic granulocytic leukemia (7.89 /- 3.56 micrograms/ml), myelodysplastic disorders (9.25 /- 4.73 micrograms/ml), and acute nonlymphocytic leukemia (3.85 /- 3.50 micrograms/ml) as compared to normal (5.63 /- 1.42 micrograms/ml). Among patients with lymphoproliferative disorders, the mean level was normal in lymphoma (5.73 /- 2.59 micrograms/ml), multiple myeloma (5.47 /- 1.31 micrograms/ml), and hairy cell leukemia (7.04 /- 3.69 micrograms/ml). The serum TR was significantly elevated in chronic lymphocytic leukemia (CLL; 14.17 /- 12.29 micrograms/ml), and the serum levels reflected the clinical stage of the disease. These findings suggest that serum TR measurement may provide a useful laboratory index of disease activity in certain disorders such as CLL, whereas it most likely reflects the intensity of erythropoiesis in the remaining hematological disorders that were evaluated in this study.- - - - - - - - - - ranking = 0.29547372330982keywords = myelodysplastic (Clic here for more details about this article) |
5/18. Hematologic malignancies associated with primary mediastinal germ-cell tumors.Three men with primary mediastinal germ-cell tumors subsequently developed a malignant hematologic disorder characterized by pancytopenia and marrow infiltration with hematopoietic blast cells. Two of these patients were classified as having acute megakaryocytic leukemia and the third was believed to have a myelodysplastic syndrome with a prominent megakaryocytic component. Analysis of clinical characteristics of these patients and review of the literature suggest that the proximate association of mediastinal germ-cell tumors with malignant hematologic disorders is neither a coincidence nor a consequence of chemotherapy given for the germ-cell tumor. We believe this association represents the evolution of a neoplastic disorder that initially involves a totipotent germ cell. These germ cells, when located in the mediastinum, apparently acquire hematologic phenotypes and are manifested clinically as a hematologic malignancy.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
6/18. A myelodysplastic syndrome with marrow eosinophilia terminating in acute nonlymphocytic leukemia, associated with an abnormal chromosome 16.A patient presented with a myelodysplastic syndrome and bone marrow eosinophilia that evolved six months later into an acute nonlymphocytic leukemia (ANLL). Cytogenetic analyses of the bone marrow revealed 86% of the metaphases with 45,X-Y,inv(16)(p13;q22),t(11;17) (q11;q25),del(21)(q13) and 14% of the metaphases with the same abnormalities but with a y chromosome. The association of ANLL, bone marrow eosinophilia, and abnormal chromosome 16 has previously been reported and has been suggested to have a favorable prognosis. Our patient is unique in that ANLL was preceded by a preleukemic phase associated with bone marrow eosinophilia. When complete remission was achieved, the bone marrow cytogenetics returned to normal, and the eosinophilia disappeared.- - - - - - - - - - ranking = 5keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
7/18. myelodysplastic syndromes in childhood: three case reports.Three children with myelodysplastic syndromes (MDS) are described following the diagnostic criteria proposed by the FAB-cooperative group. Two of the children were of Turkish origin. Two cases fit the criteria for 'refractory anaemia with excess of blasts in transformation'. The other one is most consistent with 'chronic myelomonocytic leukaemia'. The patients received 'ANLL type' induction. One died during induction, two were grafted, of whom one survives.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
8/18. Concurrent myelodysplasia and lymphoproliferation: a disorder of the true pluripotential stem cell?The lymphoproliferative disorders and the myelodysplastic syndromes are thought to result from the clonal expansion of a single abnormal precursor cell. Seven patients who were found to have concurrent myelodysplasia and lymphoproliferation are described. In all cases myelodysplasia and lymphoproliferation were diagnosed simultaneously or myelodysplasia preceded overt lymphoproliferation by a brief interval. Thus, myelodysplasia in these patients was not related to treatment given for a lymphoproliferative disorder. Stem cell theory is reviewed with special reference to evidence for an adult human stem cell common to both haemopoietic and lymphoid cell lines (CFU-L-M). The presence of concurrent myelodysplasia and lymphoproliferation in these seven patients may be the result of the clonal expansion of an abnormal pluripotential stem cell. It may be possible in some cases to achieve remission of the lymphoproliferative disorder with return of normal haematopoiesis if residual normal stem cells are present and repopulate the marrow following cytotoxic therapy.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
9/18. Studies on mitochondrial and cytoplasmic malate dehydrogenase in childhood myelodysplastic syndrome.Three cases of uncommon childhood hematologic disorders are reported. At presentation, one patient had refractory anemia with an excess of blasts (RAEB) with partial 7-monosomy and was reclassified into RAEB "in transformation" thereafter. Another case was diagnosed as acute myelogenous leukemia with complete 7-monosomy. The other case was diagnosed as RAEB "in transformation" without chromosome aberrations. The cytogenetic studies of the patients with 7-monosomy revealed abnormal karyotypes on bone marrow cells, but normal karyotypes on peripheral blood cells. Polymorphonuclear cells from the two patients with 7-monosomy revealed reduced mitochondrial malate dehydrogenase activity, but those from the patient with RAEB "in transformation" without chromosome aberrations did not. Cytoplasmic malate dehydrogenase activity, having been defined as located on chromosome 2, was within the normal range in those three patients. The decreased mitochondrial enzyme activity in the two patients with 7-monosomy would be a dosage effect of the chromosome aberration, but not caused by their hematologic disorders. The level of mitochondrial enzyme activity in the patients with 7-monosomy was reduced in polymorphonuclear cells, but not in mononuclear cells in peripheral blood. This fact would indicate that such chromosome evolution had involved myeloid cells only, but not lymphoid cells. Both enzymes from leukemic cells of four patients with active disease revealed much higher activities than controls, an expression of partially enhanced oxidative phosphorylation.- - - - - - - - - - ranking = 4keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
10/18. Sequential karyotypic evolutions and bone marrow aplasia preceding acute myelomonocytic transformation from myelodysplastic syndrome.Serial haematopathological and cytogenetic studies disclosed three distinct clinical phase in a case of refractory anaemia (RA), a subtype of myelodysplastic syndrome (MDS; FAB group, 1982): first, chronic MDS phase (1 year 10 months) with karyotypic abnormality (45, XY, --7) (Clone I); second, hypo-aplastic phase concurrent with first clonal evolution (45, XY, --7, 12p--) (Clone II); third, acute myelomonocytic leukaemia phase (6 months) with second clonal evolution (45, XY, --7,t (1q --; Bq ), Bq --, 12p --) (Clone III). In the second phase the bone marrow became almost aplastic as Clone II expanded progressively, indicating simultaneous occurrence in Clone II stem cells of growth advantage for self-renewal function over Clone I and normal stem cells, and arrest of differentiation. These observations support the hypothesis that leukaemic change in MDS, at least in RA, occurs by stepwise clonal evolution(s), not by progressive arrest of differentiation in original MDS clone.- - - - - - - - - - ranking = 5keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
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