Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromosomal in situ suppression (CISS) hybridization was performed with library DNA from sorted human chromosomes 8, 9, 15, 17, 21, and 22 on immunologically stained bone marrow cells of four patients with a hematologic neoplasm, including two patients with myelodysplastic syndrome and trisomy 8, one patient with promyelocytic leukemia bearing the translocation t(15;17)(q22;q11-12), and one patient with chronic myeloid leukemia and the translocation t(9;22)(q34;q11). In all patients, the results of conventional karyotype analysis could be confirmed by one- or two-color CISS hybridization using the appropriate chromosome-specific libraries. Our results show that CISS hybridization can detect both numerical and structural chromosome changes in immunologically classified cells with high specificity and reliability. The fact that chromosome spreads of very poor quality can now be included in such analyses is a decisive advantage of this approach. In addition, the suitability of this approach for interphase cytogenetics is discussed.
 ...
PMID:Chromosomal in situ suppression hybridization of immunologically classified mitotic cells in hematologic malignancies. 137 13

Monoclonal antibodies (McAbs) against a part of v-myb gene product were prepared for the detection of human c-myb gene product (p75c-myb). Western blotting analyses with these McAbs were performed on human leukemia-lymphoma cells. All T-cell lines were positive in p75c-myb expression. B-cell lines were variable, myeloid and erythroid cells were positive although the amount of expressed p75c-myb was less than the T-cell lines. Cells isolated from patients were positive in expression except for cells from acute myeloblastic leukemia with maturation (AML M2), acute hypergranular promyelocytic leukemia (AML M3) and erythroleukemia (AML M6) developed from myelodysplastic syndromes. Differences in p75c-myb expression seemed to depend upon the differentiation stage and distinctive lineage from which each cell line had been established. The p75c-myb expression in HL60 (acute promyelocytic leukemia cell line) showed remarkably high at logarithmic growth. When examined with HL60, p75c-myb expression significantly decreased during the differentiation induced by 12-O-tetradecanoylphorbol-13-acetate or retinoic acid. These results suggest that p75c-myb expression plays a crucial role in hematopoietic cell proliferation and differentiation and that multiple mechanisms including aberrant expression of p75c-myb is involved in leukemogenesis.
 ...
PMID:p75c-myb expression in leukemia-lymphoma cells correlated with proliferation and differentiation. 218 45

Expression of three clones (6-1E, 7-3G and 9-5C) selected from a chronic lymphocytic leukemia cDNA library was studied by nucleic acid hybridization in human promyelocytic leukemia cells (HL-60) treated with chemical inducers of cell differentiation and in primary cells derived from 27 patients with leukemia or myelodysplastic syndrome. The differentiation of HL-60 cells into macrophage-like cells upon induction by 12-0-tetradecanoyl phorbol-13-acetate (TPA) was accompanied by rapid induction of the expression of 6-1E and 7-3G genes. The levels of expression of the 9-5C gene were not altered during macrophage-monocytic or granulocytic differentiation of HL-60 cells. The expression of the 6-1E and/or 7-3G gene was induced by TPA in four of 6 samples derived from patients who achieved complete remission, but not in any of the acute nonlymphocytic leukemia samples from patients who failed to achieve complete remission. These findings suggest that expression of the 6-1E and 7-3G genes is related to macrophage-monocytic differentiation and that alterations of these gene expressions in fresh leukemia cells after one hour of TPA treatment are of prognostic significance in predicting the response to therapy.
 ...
PMID:Expression of selected genes in differentiated HL-60 cells and primary cells from human leukemias. 233 84

The active metabolite of vitamin D known as 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is a major physiologic regulator of mineral metabolism in man. The compound is also a potent inducer of differentiation of a human promyelocytic leukemia cell line known as HL-60. The induction of differentiation of myeloid leukemia cells to functional end cells offers an appealing therapeutic prospect. We investigated the ability of 1,25(OH)2D3 both to induce in vitro the differentiation of blast cells taken from patients with acute myelogenous leukemia and to improve hematopoiesis in vivo in patients with the myelodysplastic syndromes (preleukemia). We found that high concentrations (10-6 M) of 1,25(OH)2D3 significantly induced the in vitro differentiation of blast cells as measured by morphology, phagocytosis, and superoxide production. A concentration of 10-9 M 1,25(OH)2D3 had no effect on blast cell differentiation. We gave 2 microgram/day of 1,25(OH)2D3 to 18 patients with myelodysplastic syndrome (preleukemia) in an attempt to improve their hematopoiesis. During therapy, their peak peripheral blood granulocyte, platelet, and macrophage concentrations were slightly elevated as compared to their baseline, starting levels. Eight patients had a partial or minor peripheral blood response to the compound during the administration of 1,25(OH)2D3. However, no patient showed significant improvement of peripheral blood cell or marrow blast cell counts by the end of the study (greater than or equal to 12 weeks) as compared to their starting levels. Seven of the patients developed leukemia before or by 12 weeks of treatment. Nine of the 18 patients developed hypercalcemia. Taken together, the study shows that high concentrations (10-6M) of 1,25(OH)2D3 can induce differentiation of leukemia blast cells in vitro, but the administration of 1,25(OH)2D3 to patients with the myelodysplastic syndromes (preleukemia) does not have an enduring therapeutic effect. Hypercalcemia prevented administering greater amounts of 1,25(OH)2D3. In the future, the use of new vitamin D analogs that induce hematopoietic cell differentiation without inducing hypercalcemia might allow the achievement of higher blood levels of the inducing compound and might be medically useful for selected preleukemic and leukemic patients.
 ...
PMID:1,25-Dihydroxyvitamin D3: in vivo and in vitro effects on human preleukemic and leukemic cells. 241 38

Recently, a novel approach has been used in the treatment of leukemia: induction of the leukemic cells to undergo terminal differentiation. Based on its in vitro ability to induce differentiation in several myeloid leukemic cell lines, retinoic acid (RA) has been applied clinically in cases of myelodysplastic syndromes and acute myeloid and promyelocytic leukemia. In the present study we have determined in detail the ability of RA to induce expression of granulocytic functions in a human promyelocytic leukemia cell line (HL-60) and compared it with that of dimethylsulfoxide (DMSO). Several granulocytic characteristics (phagocytosis, surface adherence and generation of free radicals in response to phorbol-ester) were induced to the same degree by both agents. Other normal neutrophil functions, including lysozyme accumulation, spontaneous migration, chemotactic activity toward zymosan-activated serum (containing C5a), the peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and spontaneous motility in semi-solid medium were induced by DMSO, but they were absent or incompletely expressed in RA-induced cells. In contrast, only RA induced migration toward leukotriene B4 (LTB4). Simultaneous treatment with RA and DMSO proved synergistic with respect to morphological maturation and several functions (e.g. NBT reduction), but complementary stimulation of other activities (e.g. chemotaxis, lysozyme content) could not be demonstrated. Furthermore, characteristics induced by DMSO (i.e., expression of C5a and FMLP receptors and accumulation of lysozyme) were inhibited by the addition of RA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Expression of granulocytic functions by leukemic promyelocytic HL-60 cells: differential induction by dimethylsulfoxide and retinoic acid. 347 6

The relation between the quantified French-American-British cooperative study (FAB) classification and presenting features was studied in 123 adult patients (greater than or equal to 15 years) with acute myeloid leukemia. Myeloblastic leukemia with maturation (M2) patients with a high maturation index (M2a) were older, compared to the other myeloblastic subgroups, while promyelocytic leukemia (M3) patients were younger than those with M2 or M2a. Differences between various leukemia types were found in the occurrence of a preceding myelodysplastic syndrome, leukocyte count, and platelet count. In both monoblastic leukemia (M5) and myeloblastic leukemia (M1-3) a smaller degree of maturation seemed to be related to a larger tumor mass. The effect of chemotherapy was analyzed in a group of 64 patients. Comparison between immature (M1) and more mature (M2) myeloblastic leukemia suggested a longer duration of first complete remission and a longer survival in M2. The findings of this study may imply that the degree of maturation determines tumor mass and the success of chemotherapy.
 ...
PMID:Clinical and laboratory data related to maturation in acute leukemia. 658 98

The malignant cells of acute promyelocytic leukemia (APL) contain a reciprocal chromosomal translocation that fuses the promyelocytic leukemia gene (PML) with the retinoic acid receptor alpha gene (RAR alpha). To test the hypothesis that the chimera PMLRAR alpha plays a role in leukemogenesis, we expressed a PMLRAR alpha cDNA in myeloid cells of transgenic mice. PMLRAR alpha transgenic mice exhibited impaired neutrophil maturation early in life, which progressed at a low frequency over the course of several months to overt APL. Both the preleukemic state and the leukemia could be transplanted to nontransgenic mice, and the transplanted preleukemia could progress to APL. The APL recapitulated features of the human disease, including a response to retinoic acid. Retinoic acid caused the leukemic cells to differentiate in vitro and in vivo, eliciting remissions of both the preleukemic state and APL in mice. Our results demonstrate that PMLRAR alpha impairs neutrophil differentiation and initiates the development of APL. The transgenic mice described here provide an apparently accurate model for human APL that includes clear evidence of tumor progression. The model should be useful for exploring the molecular pathogenesis of APL and the mechanisms of the therapeutic response to retinoic acid, as well as for preclinical studies of therapeutic regimens.
 ...
PMID:A PMLRARalpha transgene initiates murine acute promyelocytic leukemia. 912 33

Isovaleric acidemia, an autosomal recessive disorder, is due to isovaleryl-coenzyme A dehydrogenase deficiency and is one of the branched-chain aminoacidopathies. Isovaleric acidemia may present in the neonatal period with an acute episode of severe metabolic acidosis, ketosis, and vomiting and may lead to coma and death in the first 2 months of life. This report concerns an infant who presented at 10 days of age because of lethargy, poor feeding, hypothermia, cholestasis, and thrombocytopenia, leukopenia, and profound pancytopenia. Death occurred at 19 days of age. Autopsy showed mild fatty change in the liver and extramedullary hematopoiesis, generalized Escherichia coli sepsis, and myelodysplasia of the bone marrow with arrest of the myeloid series at the promyelocytic stage. The appearance resembled promyelocytic leukemia, but the diagnostic 15:17 translocation was not present. The maturation arrest in granulopoiesis in isovaleric acidemia appears to be most likely due to a direct metabolic effect on granulocyte precursor cells.
 ...
PMID:Isovaleric acidemia with promyelocytic myeloproliferative syndrome. 1019 53

Acute myeloblastic leukemia represents a heterogeneous group of diseases. The diagnosis and prognosis is most accurately provided by pretreatment assessment of the clonal molecular genetic derangement responsible for the disease, often provided by cytogenetic analysis. Other prognostic features include patient age, antecedent myelodysplasia, prior chemotherapy, and the presence of FLT-3 mutations. Accurate assessment of prognosis permits a risk-adapted treatment approach to maximize probability of cure and minimize treatment-related toxicity. The majority of patients with promyelocytic leukemia with the PML/RARalpha fusion gene can be cured with an all-trans-retinoic acid and anthracycline-based treatment program. All other patients are typically given cytarabine and anthracycline-containing induction regimens, although some with particularly poor prognosis disease may be more appropriate candidates for experimental induction therapies. Postinduction treatments include further conventional chemotherapy, stem cell transplant strategies, and experimental approaches. Issues pertinent in selecting treatments for patients in the different risk categories are reviewed.
 ...
PMID:Update in acute leukemia 2003: a risk adapted approach to acute myeloblastic leukemia in adults. 1512 39

Professor MA Rou has been engaged in clinical and basic research of hematology for more than 40 years. He is excel in the treatment of refractory hematological diseases under the guidance of holism and syndrome differentiation in Chinese medicine. Application of arsenic-containing Chinese herbal medicine in treating myelodysplastic syndrome (MDS), primary polycythemia vera (CMPD-PV), primary thrombocythemia (CMPD-ET), MDS-U, myeloproliferative disease, acute non lymphocytic leukemia except for promyelocytic leukemia, Prof. MA has made great innovation and exploration. For some diseases, he has obtained much mature experiences. Although some are still in the stage of exploration, ideal clinical effects has been shown primarily.
 ...
PMID:[Clinical application of professor MA Rou's experience in treating hematological disease by arsenic-containing Chinese herbal medicine]. 2191 Mar 53


1 2 Next >>