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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colony-stimulating factors (CSFs) have entered the clinical arena. Several investigators have explored, in first clinical phase I studies, different routes of administration to define the optimum biological dose, maximum tolerated dose, toxicity, and pharmacokinetics of these reagents. It has been demonstrated that recombinant human (rh) granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) can be safely administered over a broad dose range to increase number of circulating granulocytes in man. More recently, GM-CSF and G-CSF have been involved in phase Ib/II studies to assess the granulopoietic responses of patients with granulocytopenia due to various underlying disease states including myelodysplastic syndrome, aplastic anemia, cyclic neutropenia, Kostmann's syndrome, and the acquired immuno-deficiency syndrome. Both factors were also investigated with respect to their potential to prevent chemotherapy induced granulocytopenia or to accelerate recovery from that condition. The short-term effects of rh GM-CSF after autologous bone marrow transplantation for various solid tumors and lymphoid malignancies were assessed as well. In this article we will focus on recent results that have emerged from in vivo studies utilizing CSFs.
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PMID:Polypeptides controlling hematopoietic blood cell development and activation. II. Clinical results. 265 Jul 57

We have screened a large series of primary human leukemias for activating point mutations at codons 12, 13 and 61 of the N-ras and K-ras proto-oncogenes and at codons 12 and 61 of the H-ras proto-oncogene by using panels of oligonucleotide probes in conjunction with polymerase chain reaction gene amplification. 13 of 64 (20%) acute lymphoblastic leukemia cases had ras gene mutations mostly involving N-ras codon 12/13, G-A (gly-asp) transitions. Consistent with previous studies, a comparable pattern and frequency of ras mutation was found amongst 45 cases of acute myeloid leukemia and myelodysplasia. By contrast, of 30 cases of mature B cell chronic lymphocytic leukemia, only one in terminal prolymphocytoid transformation harboured an activated ras gene. These patterns of mutation did not correlate with ras gene methylation state, a finding not obviously compatible with differential gene accessibility being an important determinant of ras gene mutation patterns in leukemogenesis. Our data suggest that activated ras is more important in tumourigenesis of immature than mature lymphocyte progenitors whilst similar mechanisms associated with aetiology and/or target cell susceptibility probably underlie the similar patterns of ras gene mutations seen in acute leukemias of both myeloid and lymphoid cell lineages.
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PMID:Analysis of ras gene mutations and methylation state in human leukemias. 266 44

In order to maintain adequate circulating numbers of blood cells, the bone marrow must produce billions of cells each day and must be able to rapidly increase production by 10-20-fold in response to infection and hemorrhage. The existence of circulating factors that regulate this process has been suspected for over 100 years. Recently, the genes encoding these growth factors were cloned and their functions are now identified. Interleukin-3 (IL-3) acts on the most primitive hematopoietic stem cell, driving this self-renewing cell to produce progeny of all hematopoietic lineages. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the granulocyte-macrophage progenitor cell, as well as cells committed to the erythroid lineage, to differentiate. G-CSF and M-CSF stimulate the most differentiated myeloid progenitors to produce granulocytes and monocytes/macrophages, respectively. Erythropoietin stimulates the differentiation of late erythroid progenitors. In the lymphoid progenitor lineage, IL-2 stimulates T cell differentiation; IL-4 and IL-6 stimulate differentiation of B cells. The colony-stimulating factors also enhance function and cause activation of the mature cells whose production they induce. In clinical trials, these hormones have successfully ameliorated anemia in renal failure, chronic disease, and in prematurity. They have improved pancytopenias in aplastic anemia, myelodysplastic syndromes, and congenital cytopenias, and they have hastened recovery from chemotherapy and bone marrow transplantation.
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PMID:Hematopoietic hormones: from cloning to clinic. 267 59

We report on six cases of 6p rearrangement in various haematological malignancies. On reviewing the literature, we assume 6p rearrangements to be secondary anomalies in both myeloid and lymphoid malignancies, and confirm it to be strongly associated with -5/del (5q) in myelodysplastic syndromes.
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PMID:Chromosome 6p rearrangements appear to be secondary changes in various haematological malignancies. 279 78

The authors studied 35 marrow biopsies from 32 patients with rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disease, polymyositis, and psoriatic arthritis. Reasons for biopsy included cytopenia, fever of unknown origin, and malignancy. Cellularity was abnormal in 71%. Plasma cells were increased in 60% and associated with lymphoid aggregates. Immunoperoxidase stains showed polyclonal perivascular plasma cells and increased T-cells forming lymphoid aggregates. Two patients had granulomas without documented infection. Anemic patients had findings consistent with anemia of chronic disease, erythroid aplasia, hemolysis, and iron deficiency. Iron stores were variable. Platelet and granulocyte precursors were variably altered and did not predictably correlate with the presence, absence, or cause of thrombocytopenia and neutropenia. Myelodysplastic syndromes were present in two patients with rheumatoid arthritis. Osteomalacia and osteoporosis were seen, resulting from renal failure and steroids. Marrow findings are unpredictable and reflect the diverse causes of cytopenias in patients with connective tissue disorders.
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PMID:Bone marrow findings in connective tissue disease. 281 17

Sixty cats with hematologic abnormalities indicative of non-lymphoid hematopoietic neoplasia were classified into two groups, myelodysplastic syndromes (MDS) and acute myelogenous leukemias (AML), using criteria developed for human patients with similar diseases. Cats with myeloblast counts in bone marrow of less than 30% were classed as MDS and cats with myeloblast counts of 30% or greater were classed as AML. The clinical, laboratory, and postmortem findings in each group were described and compared. Clinical signs of disease were similar in both groups, the most common being inappetance, lethargy, and weakness. Non-regenerative anemia, macrocytosis, neutropenia, and thrombocytopenia were frequent hemogram abnormalities in both groups. Diagnostically useful differences in physical and peripheral blood findings were a higher prevalence of splenomegaly and/or hepatomegaly, thrombocytopenia, and severe anemia in the AML group. Circulating myeloblasts were found only in cats in the AML group. Outcome of disease was similar in both groups; 85% of the cats in each group died or were euthanatized within one week of diagnosis. In cats that were necropsied, extramedullary leukemic infiltrates were found in all cats in the AML group and in none of the cats in the MDS group.
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PMID:Non-lymphoid hematopoietic neoplasia in cats: a retrospective study of 60 cases. 282 80

Bone marrow sections from 44 cats with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) were graded for reticulin content using light microscopic methods. Twenty-seven (61%) of the cats had slight to marked reticulin myelofibrosis. The association of myelofibrosis with possible pathogenetic factors, including megakaryocyte count, intramedullary lymphoid follicles, hemosiderin content, and FeLV antigenemia, was examined. No evidence was found that indicated a causal relationship between myelofibrosis and any of these factors.
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PMID:Myelofibrosis in cats with myelodysplastic syndrome and acute myelogenous leukemia. 283 59

Peripheral blood cells from patients with myelodysplastic syndromes were assayed for B-cell and immunoregulatory T-cell functions. The B/T cell ratio in myelodysplastic patients (n = 11) was significantly higher than in controls (n = 12). These patients had a reduction in total T-cell (OKT3+) frequency and in T-cell subset (OKT4+/OKT8+) ratios. The response of patients' cells to both pokeweed mitogen (PWM) and phytohemagglutinin (PHA) was reduced, but patients' B cells responded normally to stimulation with Staphylococcus aureus Cowan (SAC). The levels of IgG and IgM detected in 7-day culture supernatants of PWM-stimulated patient and control cells were similar. Normal B-cell and immunoregulatory T-cell functions were subsequently demonstrated in allogeneic co-culture combinations of enriched T and B cells from patients and controls. The data presented indicate that the frequent infections of myelodysplastic patients are not causally related to impaired humoral mechanisms. The data also favor the possibility that the stem cell disorder in these syndromes is functionally expressed at a subsequent stage to the lymphoid differentiation pathway.
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PMID:Immunoglobulin synthesis in myelodysplastic syndromes: normal B-cell and immunoregulatory T-cell functions. 287 58

A 57-year-old female developed myelodysplastic syndrome (MDS) that terminated as a biphenotypic leukemia after exposure to chemoradiotherapy. Double staining of blast cells, using monoclonal antibodies specific for myeloid and lymphoid lineage, demonstrated that one-third of the leukemic cells simultaneously expressed the E rosette-associated antigen (OKT11) and myeloid-associated antigen (MY7). This finding suggests the possibility that some cases of MDS are clonal disorders that arise in a pluripotent stem cell that can also differentiate to T cell lineage.
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PMID:Simultaneous expression of lymphoid and myeloid phenotypes in acute leukemia arising from myelodysplastic syndrome. 316 79

34 patients with primary myelodysplastic syndrome (MDS), initially diagnosed as subtypes refractory anaemia (RA) and RA with ringed sideroblasts (RA-S), were followed to investigate the distribution of lymphoid and myeloid differentiation antigens in the blood and bone marrow in search of potential prognostic significance with regard to progression to RA with an excess of blasts (RAEB) or acute myeloid leukaemia, and for relations to clinical, morphological and cytogenetic findings. Patients who later progressed to RAEB had significantly decreased percentages of anti-T8 positive T-suppressor cells in the blood at diagnosis compared to those who did not (p = 0.05). Sequential analysis showed a decrease with time also in the percentages of anti-T8-positive cells (p = 0.05). In the bone marrow, progressing patients initially showed significantly increased percentages of anti-My9-positive immature myeloid cells (p less than 0.001), and the percentages of anti-My9-positive cells in the bone marrow increased with time (p less than 0.005). Analysis of the pooled data revealed a statistically significant relation between increasing percentages of anti-My9-positive cells and the frequencies of clonally abnormal (p less than 0.001) and abnormal (p = 0.004) metaphases.
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PMID:Analysis of leucocyte differentiation antigens in blood and bone marrow in patients with refractory anaemia (RA) and RA with sideroblasts. Prognostic implications of sequential and follow-up data. 319 23


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