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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood T lymphocytes obtained from two patients with paroxysmal nocturnal hemoglobinuria (PNH) were immortalized with human T-lymphotropic virus type 1 (HTLV-1). These cells showed interleukin-2 (IL-2)-dependent cell growth in culture. Cell surface analysis showed that they had the phenotype of a helper/inducer T subset that was positive for CD2, CD3, and CD4, but negative for CD8, similar to adult T-cell leukemia cells induced by HTLV-1. These cell lines lacked glycosylphosphatidylinositol (GPI)-anchored proteins, CDw52, CD55 (decay-accelerating factor; DAF), and CD59 on the cell surface, whereas intracellular DAF protein was detected. These T-subset cell lines with a PNH phenotype did not synthesize GPI anchor, whereas a control cell line, similarly prepared from the T cells of a healthy volunteer, produced the anchor. The control cells expressed CDw52, DAF, and CD59 on the cell surface and showed the phenotype of a helper/inducer subset. Southern blot analysis confirmed the clonality of each cell line. These CD4+ T-cell lines with a PNH phenotype and a subset-matched control counterpart could be a useful model for PNH investigation.
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PMID:Interleukin-2-dependent T-cell lines established from paroxysmal nocturnal hemoglobinuria patients. 751 13

In order to distinguish various types of MDS, such as RA/AA, RA/ITP or RA/HA, from AA, ITP or HA, bone marrow (BM) cells were studied by using cytogenetic techniques including R-banding karyotypic analysis and sister chromatid differentiation (SCD) assay in 334 cases of hematological diseases (160 MDS, 54 RA/AA, RA/ITP or RA/HA; 60 AA, 3 other known anemias, 38 PNH and 19 ITP). The results showed: (1) karyotypes and SCD values were both normal in more than 90% of AA, PNH, ITP and other known anemias, but they were both abnormal in about 35.6% of MDS and only 13.0% of RA/AA, RA/ITP or RA/HA. These results indicated that cytogenetic techniques were useful in hematological clinic and that RA/AA, or RA/ITP or RA/HA might be pre-RA or atypic RA. This was supported by the results of following up on some RA/AA, RA/ITP or RA/HA cases, (2) clonal abnormal karyotypes were found in 64.4% of MDS. The recurrent chromosomal alterations were +8, 20q-, -5/5q-, -7/7q-, similar to those reported in literatures. (3) 16 MDS cases were followed up and 15 MDS with SCD negative, but one with SCD positive developed leukemia in our hospital. It is suggested that change from SCD positive to negative was indicative of malignant transformation of BM cells. This was supported by the results of cytogenetic analysis in RA/AA, RA/ITP, RA, RAEB, RAEBT and leukemias. (4) Because more structural chromosome alterations occur in SCD negative than SCD positive MDS, the numerous chromosome alterations (monosomy) might occur in earliest development of MDS into leukemias.
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PMID:[Cytogenetic studies on 334 myelodysplastic syndrome (MDS), aplastic anemia (AA) and other hematological diseases]. 760 Aug 65

We performed a flow cytometric analysis using monoclonal antibodies to decay accelerating factor (DAF) and CD59/membrane attack complex inhibitory factor (CD59/MACIF) in order to investigate the leukemic cells and erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria (PNH) who developed acute myelocytic leukemia. In May 1990, the leukemic cells comprised 70% of the mononuclear cells in the bone marrow and 76% of those in the peripheral blood. They consisted of a mixture of positive and negative populations, including single DAF-positive cells. In August 1990, almost 100% of the peripheral mononuclear cells were leukemic blasts, and these consisted of a single population with reduced DAF expression. Single-color flow cytometric analysis showed that the leukemic cells lacked CD59/MACIF, while control leukemic cells (n = 3) expressed both DAF and CD59/MACIF. Leukemic blasts from this patient and six control patients expressed lymphocyte function-associated antigen 3 and FcIII receptors (CD 16) both before and after treatment with phosphatidylinositol-specific phospholipase C. The patient's erythrocytes lacking DAF and CD59/MACIF expression corresponded to the proportion of complement-sensitive cells at the onset of acute leukemia. These DAF- and CD59/MACIF-deficient erythrocytes disappeared almost completely with progression of the leukemia. In conclusion, it appears that the expression of glycosylphosphatidylinositol-linked membrane proteins by leukemic cells was heterogeneous and discordant in our patient, and that the leukemic cells were derived from the PNH clone because of their deficiency of CD59/MACIF. It is also suggested that DAF could compete more effectively than CD59/MACIF for a limited number of anchor molecules available on the proliferating leukemic cells.
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PMID:Discordant and heterogeneous expression of GPI-anchored membrane proteins on leukemic cells in a patient with paroxysmal nocturnal hemoglobinuria. 768 3

Flow cytometric analysis of blood cells is an important technique for the evaluation of the immunological functions of patients with various disorders, and also for the differential diagnosis of leukemias. In the lymphocyte subset analysis, special attention should be paid to the optimal gating of lymphocytes. We recommend the use of CD13 and CD33 to ascertain more accurate gating of lymphocytes and more efficient monitoring of the contamination of non-lymphoid cells, especially in patients with PNH, in addition to CD45 and CD14, which are already utilized routinely. We also feel that 2-color and 3-color analyses should be applied more frequently for the routine laboratory tests for lymphocyte subsets. With regard to the analysis of leukemia cells, the combined use of nuclear DNA content or TdT (terminal deoxynucleotidyl transferase) with other routine cellular markers is quite useful for the analysis of a small number of leukemia cells, and enables the differentiation of leukemia cells from the contaminating non-malignant cells, particularly in the analysis of the minimal residual diseases. Among the cellular markers defined by specific monoclonal antibodies, we stress the physiological significance of recently developed cell adhesion molecules, such as selectins and their carbohydrate ligands, which are closely involved in the recruitment of leukocytes in inflammatory responses, as well as in the infiltration processes of leukemia cells.
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PMID:[Flow cytometry in clinical laboratory medicine]. 825 77

In paroxysmal nocturnal hemoglobinuria (PNH), little is known about the molecular events leading to the clinical manifestations except for the hemolysis. To unfold the complex pathophysiology, it is necessary to elucidate the nature of the PNH clone. PNH exhibits an acquired stem cell disorder, a clonal expansion of affected cells, concomitant depression of normal hematopoiesis in bone marrow (BM), and, although infrequently, the development of leukemia. The PNH clone is thus expected to exhibit some neoplastic features. We report here that CD34+ hematopoietic progenitor cells of PNH-BM yielded blood cells of three lineages with PNH phenotype alone when transplanted into sublethally irradiated severe combined immunedeficient mice. The hematopoiesis persisted for more than 10 months and did not always need human cytokines. In contrast, the hematopoiesis by control grafts obtained from healthy volunteers required an intense cytokine treatment. This in vivo model defines the preferential hematopoiesis of pluripotent PNH progenitor cells, indicating the intrinsic growth abnormality of PNH clone.
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PMID:Preferential hematopoiesis by paroxysmal nocturnal hemoglobinuria clone engrafted in SCID mice. 865 6

The membrane expression of nine glycosyl phosphatidyl inositol (GPI)-linked molecules was analyzed by flow cytometry on circulating cells from 18 patients affected by paroxysmal nocturnal hemoglobinuria (PNH). The results allowed us to select CD66b, CD14, CD59, CD24 and CD59 monoclonal antibodies as the most suitable reagents for discriminating between normal and PNH cells in PMN, monocytes, RBC and B or T lymphocytes, respectively. In order to assess whether the analysis of distinct cell populations could provide differential information on the extent of the disease, we compared the proportion of residual normal cells in RBC, monocyte and PMN populations. The mean percentage of unaffected cells was higher in RBC as compared to PMN (50.5 +/- 18.7 vs 17.7 +/- 19.7, P < 0.0001). The proportion of normal PMN was, in turn, significantly greater than that of normal monocytes (17.7 +/- 19.7 vs 8.7 +/- 11.0; P < 0.05). The percentage of CD14+ monocytes was directly related to Hb concentration and platelet (Plt) count, and inversely to percent lysis at the Ham's test. The percentage of CD66b+ PMN was directly related to Plt count and Hb level, while the percentage of CD59+ RBC was associated, in an inverse fashion, only to the Ham's test. No significant correlation was found between cell marker expression and PMN count, reticulocytosis, bilirubin and serum LDH. By dividing the patients into two groups, according to high (> 10 percent) or low (< 10 percent) percentage of CD14+ monocytes, a statistical analysis showed that the main hematological parameters were significantly different.
Leukemia 1996 Aug
PMID:Blood cell flow cytometry in paroxysmal nocturnal hemoglobinuria: a tool for measuring the extent of the PNH clone. 870 38

Paroxysmal nocturnal haemoglobinuria (PNH) terminating in acute leukaemia (AL) is an infrequent condition. In several cases, flow cytometric analysis of glycosylphosphatidylinositol anchored membrane proteins such as DAF and CD59/MACIF has suggested the leukaemic cells to be derived from the PNH clone, thereby implicating PNH as a potential preleukaemic disease. In the present paper, we review the data for one patient treated in our hospital and 20 cases reported in the literature from 1969 to 1993. The sex ratio is 1 female/2 males, mean age at diagnosis of PNH was 46 years and the mean interval between the diagnoses of PNH and AL was 53 months. AL type was AML M6 in 8 patients, other types of AML in 12 and ALL in one, with a mean survival of 7.1 months following diagnosis of AL. In all cases analyzed, the PNH phenotype of erythrocytes disappeared with progression of AL, whereas reappearance of this phenotype with complete remission of AL was inconstant. PNH would thus appear to be a potential preleukemic disease. When this disorder terminates in AL, the type is often AML M6, although ALL is also possible. The prognosis of AL in PNH is poor as for other secondary leukaemias. Apart from marrow aplasia, leukaemic transformation is another life threatening complication of PNH which may justify allogeneic bone marrow transplantation (allo-BMT) and potential leukaemic transformation can therefore be an additional argument in favour of allo-BMT when pancytopenia develops in PNH patients.
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PMID:Acute leukaemia in paroxysmal nocturnal haemoglobinuria. Case report and review of the literature. 897 94

Four paroxysmal nocturnal hemoglobinuria (PNH) patients with severe thrombocytopenia, hemolytic anemia and neutropenia were treated using a combination of filgrastim (G-CSF) and cyclosporin. In all patients a trilineage response of hematopoiesis was achieved. In addition, the proportion of glycosyl-phosphatidylinositol (GPI)-deficient granulocytes decreased. All patients mobilized CD34+ hematopoietic progenitors into peripheral blood after starting treatment with G-CSF. The majority of early progenitors (CD34+ CD38-) after mobilization into peripheral blood was found to be unaffected by the GPI-anchoring defect. No patient developed leukemia while under therapy. We conclude from these data that the combination of G-CSF and cyclosporin represents an efficient option for the treatment of hypoplastic PNH.
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PMID:G-CSF and cyclosporin induce an increase of normal cells in hypoplastic paroxysmal nocturnal hemoglobinuria. 920 Sep 95

Paroxysmal nocturnal haemoglobinuria (PNH), aplastic anaemia (AA) and myelodysplastic syndrome (MDS) are haemopoietic stem cell disorders. These disorders have some features in common, and a percentage of cases progress to acute leukaemia. We speculated that changes in gene stability are involved in the pathogenesis of these haemopoietic stem cell disorders. Therefore we investigated in vivo mutation frequencies in these disorders by erythrocyte glycophorin A (GPA) mutation assay. The assay enumerates NO or NN variant cells in 106 erythrocytes of the MN type using a flowcytometric technique. Patients undergoing chemotherapy known to be at risk of hypermutageneity were also studied. Events exceeding the 95th percentile of healthy donors (> or = 32 and 34 events, respectively for NO and NN variants) were defined as abnormal. Abnormal events in the NO variants were found in three out of seven patients undergoing chemotherapy, two out of nine patients with AA, two out of seven patients with MDS, and four out of nine patients with PNH. Abnormal events in the NN variants were found in three out of seven patients undergoing chemotherapy, two out of nine patients with AA, one out of seven patients with MDS, and two out of nine patients with PNH. These results suggest that not only PIG-A, but also other genes including the GPA gene, are hypermutable in haemopoietic stem cell disorders, and that mutagenic pressure and/or gene instability can contribute to the pathogenesis of these disorders.
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PMID:Increased frequency of somatic mutations at glycophorin A loci in patients with aplastic anaemia, myelodysplastic syndrome and paroxysmal nocturnal haemoglobinuria. 926 37

Aplastic anemia is a disease that presents with a hypocellular marrow and peripheral blood pancytopenia. In Europe and the United States, it has an age-adjusted incidence per million population per year of 2.2 compared to 11.0 in Japan and Korea. Pathogenic mechanisms are varied and include intrinsic defects of hematopoietic stem cells, defects in the marrow microenvironment, and abnormal humoral or cellular immune control of hematopoiesis. In most patients, aplastic anemia is of unknown etiology, whereas in some, the disease can be related to infections, drugs and chemicals, and hereditary causes. Therapy for aplastic anemia includes blood component transfusions, antibiotics, androgenic steroids, and corticosteroids. With supportive care, most patients with aplastic anemia die within a year of diagnosis, and only approximately 20% of patients are surviving, although often with persisting hematologic abnormalities. The use of hematopoietic growth factors has shown, for the most part, only transient beneficial effects. More definitive therapy has been the use of immunosuppressive agents including antithymocyte globulin, cyclosporine, and cyclophosphamide. With immunosuppressive therapy, a variable proportion of patients respond to therapy, ranging from 20% to 80%. However, although responses may be frequent, long-term outlook is guarded because some patients may relapse with aplastic anemia, whereas others may go on to have a clonal disorder develop, including myelodysplasia, leukemia, or paroxysmal nocturnal hemoglobinuria. As a result, survival estimates at 15 to 18 years may be only on the order of 30%. More definitive therapy has been with transplants of hematopoietic stem cells from allogeneic donors. Transplants are carried out after high-dose immunosuppressive conditioning programs. Best current results show long-term, event-free survivals with successful allografts on the order of 90%.
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PMID:Aplastic anemia. 942 94


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