Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Serum transferrin receptor measurements in hematologic malignancies. 216 85

Northern blot analysis of RNA isolated from HL-60 cells before and after differentiation induction by TPA and DMSO showed that four MPO mRNA species (3.3, 3.1, 2.7, and 2.5 kb, respectively designated alpha 1, beta 1, alpha 2, and beta 2) are expressed in HL-60 cells. However, alpha 2 and beta 2 lack part of the 3' end sequence due to different polyadenylation sites. The steady state levels of alpha 2 and beta 2 MPO mRNA increase significantly after 1 hr of induction, while all four MPO mRNA species decrease dramatically after 10 hr of induction. Our results demonstrate that MPO gene expression is developmentally and differentially regulated. Northern blot analysis of RNA isolated from blast samples of acute myelogenous leukemia (M0-M5) and chronic lymphocytic leukemia (CLL) patients indicate that four MPO mRNA species are expressed in M1-M4 but are undetectable in M5 and CLL. Primer extension and S1 nuclease protection analysis of the MPO mRNA revealed a single transcription initiation site for the MPO gene.
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PMID:Developmental and differential regulation of human MPO gene in leukemic cells. 216 3

DNA from 161 patients with various forms of hematologic malignancies were investigated for mutations in exons 1 and 2 of the N-RAS, K-RAS and Ha-RAS gene by direct sequencing of DNA amplified in vitro by the polymerase chain reaction. Mutations involving either codons 11, 12, or 13 of the N-RAS gene were identified in 18 of the 161 patients. The relative frequencies of N-RAS gene mutations in these hematologic disorders was as follows: acute myelogenous leukemia (AML), 15%; acute lymphoblastic leukemia (ALL), 14%; myelodysplastic syndromes, 24%; and myeloid and lymphoid blast crisis of chronic myelogenous leukemia (CML), 3%. No correlation was observed between the presence of mutations and cytologic features or immunophenotype of these malignancies. Mutations involving codons 12 or 13 were equally prevalent, with a glycine to aspartic acid substitution being the most frequently encountered change. A single T-ALL case had a codon 11 mutation resulting in substitution of alanine with threonine. We failed to find mutations in exons 1 and 2 of the K-RAS or Ha-RAS genes in any case except a single AML with a mutation in codon 61 of the K-RAS gene. Also, no mutations were identified in chronic phase of CML, chronic lymphocytic leukemia. Ph1 positive ALL, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma. These results indicate that RAS mutations, especially those involving exon 1 of the N-RAS gene, are frequent only in a subset of hematologic malignancies.
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PMID:The pattern of mutational involvement of RAS genes in human hematologic malignancies determined by DNA amplification and direct sequencing. 218 88

The objective of this study was to determine the dose rate of 2',2'-difluorodeoxycytidine (dFdC) that maximizes the accumulation of the active 5'-triphosphate (dFdCTP) in circulating leukemia cells during therapy. The investigational approach was to evaluate the relationship between plasma dFdC and the accumulation of dFdCTP by circulating leukemia cells during infusion of different dFdC dose rates in the same individuals. Four patients with relapsed leukemia were treated weekly with two or three consecutive infusions of 800 mg/m2, the first administered over 1 h, the second over 2 h, and the third over 3 h. Two patients, one with acute myelogenous leukemia and one with acute lymphocytic leukemia, received all three infusions, but thrombocytopenia prohibited infusion of the third dose to two patients with chronic lymphocytic leukemia. The average steady-state plasma dFdC levels, achieved within 15 min after the infusion began, were 43.8 microM during infusion of 800 mg/m2/h, 9.4 microM during infusion of 400 mg/m2/h, and 5.6 microM at 267 mg/m2/h. The median area under the concentration times time curve of dFdCTP in leukemia cells during infusion was increased 2.3- and 5.1-fold for the 2- and 3-h infusions, respectively. In vitro incubations of leukemia cells from the four patients with 2.5-100 microM dFdC for 1 h showed that the maximum cellular accumulation of dFdCTP was produced by 15-20 microM dFdC. We conclude that a dose rate of greater than 400 mg/m2/h was required to achieve plasma dFdC levels that supported the maximum rate of dFdCTP accumulation in leukemia cells.
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PMID:Pharmacologically directed design of the dose rate and schedule of 2',2'-difluorodeoxycytidine (Gemcitabine) administration in leukemia. 220 47

DNA aneuploidy (DA) was examined in adult leukemia using flow cytometry, and the method and the clinical implication of DA as a tumor marker were evaluated. The method was simple, rapid, objective, quantitative and further did not need any mitotic cells, so was proved to be very useful for screening of DA. While, DA was detected in 50 (27%) out of 185 adult cases with various types of leukemia. The frequencies of DA in the subtypes of leukemia were 55% in ATL, 26% in ALL, 17% in ANLL, 26% in CML-BC and 6% in CLL, respectively. When compared with other subtypes, the frequency in ATL was significantly higher (p less than 0.01), which suggested a special entity of this disease. In general, however, the frequency of DA in leukemia was rather low, which indicated the difficulty in application of DA by itself in diagnosis of leukemia. While, in cases with DA, DA was very useful as a tumor marker in monitoring the clinical course, for example, in the detection of early relapse or recruitment of leukemic cells. Furthermore, DA was found to be a good prognostic factor which indicates a poor prognosis in cases with ANLL and CML-BC.
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PMID:[Analysis of DNA aneuploidy as a tumor marker]. 221 64

The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and RA (retinoic acid) were investigated on the cell lines HL60 (acute promyelocytic leukemia) and K562 (erythroleukemia) and on cells from patients with several kinds of leukemia. There were 14 cases of acute lymphocytic leukemia (ALL), 2 cases of chronic lymphocytic leukemia (CLL), 23 cases of acute myeloid leukemia (M1-M7), 5 cases of chronic myelocytic leukemia in blast crisis (CML-BC) and 2 mixed leukemias. In almost all of the cases examined, after TPA exposure cells from patients with proven myeloid leukemia became adherent to the substrate, while lymphoid leukemia cells remained in suspension, allowing the differentiation of lymphoid from myeloid blasts. The only exception was in one case of CLL, which had cells that became adherent with long filamental projections. In addition, increased phagocytosis following TPA exposure permitted characterization of M7 as this was the only myeloid leukemia negative for phagocytosis. Further discrimination between the subtypes of myeloid leukemia could be based on the increased lysozyme production seen after TPA in M4 and M5. Esterase positivity allowed the discrimination of M1 cells, which were negative before and after TPA treatment. In agreement with the results of other authors, TPA and RA led to independent ways of differentiation, granulocytic-like lineage and monocytic-like cells being favored by RA and TPA, respectively. The capacity of the same cell to differentiate into more than one lineage, depending on whether RA or TPA was used, was only seen in the present study with M3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myeloid leukemia differentiation by phorbol ester and retinoic acid: a practical approach. 223 Nov 80

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.
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PMID:Expression of selected genes in differentiated HL-60 cells and primary cells from human leukemias. 233 84

We have examined the role of CMP-NeuAc:Gal beta 1-3GalNAc-R alpha(2-3)-sialyltransferase in fresh leukemia cells and leukemia-derived cell lines. Enzyme activity in normal granulocytes using Gal beta 1-3GalNAc alpha-o-nitrophenyl as substrate was 1.5 +/- 0.7 nmol/mg/h whereas activity in morphologically mature granulocytes from 6 patients with chronic myelogenous leukemia (CML) was 4.2 +/- 1.6 nmol/mg/h (P less than 0.05). Myeloblasts from 5 patients with CML in blast crisis showed enzyme activity levels of 6.5 +/- 2.5 nmol/mg/h. From 2 patients with CML, both blasts and granulocytes were obtained, with higher enzyme activity in the patients' blasts (7.1 nmol/mg/h) than in their granulocytes (4.9 nmol/mg/h) in both cases, suggesting that the increase in enzyme activity is related to the differentiation or proliferation status of the CML cells. However, similarly high enzyme levels were also seen in myeloblasts from acute myeloblastic leukemia patients (5.6 +/- 1.4 nmol/mg/h) and in some acute myeloblastic leukemia-derived cell lines (KG1a and HL60), suggesting that increased levels of this enzyme are not directly correlated with the presence of the Ph1 chromosome. This alpha(2-3)-sialyltransferase activity can also be detected in normal peripheral blood lymphocytes and exhibits increased activity in chronic lymphocytic leukemia cells and acute lymphoblastic leukemia. These data suggest that the level of enzyme activity may vary with growth rate and maturation status in myeloid and lymphoid hemopoietic cells. Finally, we have identified a glycoprotein in acute myeloblastic leukemia cells that serves as a substrate for the alpha(2-3)-sialyltransferase. The desialylated form of the glycoprotein was resialylated in vitro by the purified placental form of this alpha(2-3)-sialyltransferase and exhibits a molecular weight of about 150,000.
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PMID:Human leukemic myeloblasts and myeloblastoid cells contain the enzyme cytidine 5'-monophosphate-N-acetylneuraminic acid:Gal beta 1-3GalNAc alpha (2-3)-sialyltransferase. 237 65

The complications associated with the use of Ommaya reservoirs in 106 patients with meningeal involvement due to malignant disease are reviewed. Twenty-seven patients had acute lymphoblastic leukemia, 12 acute myelogenous leukemia, 3 chronic lymphocytic leukemia, 34 lymphoma, 29 carcinoma, and 1 chronic myelocytic leukemia. There were 11 technical complications, including 1 death due to misplacement of the catheter, 2 mild intraventricular hemorrhages, and 5 malfunctioning reservoirs; 3 required craniotomies (1 for subdural hematoma and 2 for subdural hygroma); 13 cases of bacterial meningitis occurred in 10 patients. One patient died of Staphylococcus aureus meningitis. The organisms causing the other infections were mainly coagulase-negative staphylococci (8 cases) or Propionibacterium acnes (2 cases). The projected infection rate for all patients (by Kaplan-Meier analysis) during the first year following insertion of a reservoir was 15%. Successful use of Ommaya reservoirs requires expert surgical implantation and meticulous care during accessing to minimize complications.
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PMID:Complications associated with Ommaya reservoirs in patients with cancer. The Princess Margaret Hospital experience and a review of the literature. 240 79

Cellular or proto-oncogenes are normal cellular genes important in normal cell growth and development. In some instances abnormal expression of these genes is associated with altered cell growth or with malignant transformation. Abnormalities of cellular oncogenes are common in human leukemias. These arise by multiple mechanisms such as mutation, translocation, amplification, and others. Sometimes more than one abnormality is present within a single oncogene. In other instances, a leukemia cell may contain abnormalities of several different oncogenes. Some oncogene abnormalities are relatively specific for certain leukemias and occur in almost all cases; examples include ABL in chronic myelogenous leukemia or MYC in Burkitt leukemia/lymphoma. Other abnormalities are also relatively specific but occur in only some cases such as NRAS in acute myelogenous leukemia or BCL2 in B-cell acute lymphoblastic leukemia. In other leukemias, such as most cases of acute lymphoblastic leukemia and chronic lymphocytic leukemia, oncogene abnormalities are uncommon. The precise role of oncogenes in the pathogenesis of human leukemia is unknown. Retrovirus transduced versions of some of the oncogenes modified in human leukemias cause leukemia in animals. Other oncogenes, modified or unmodified, transform animal and human hematopoietic cells in vitro. Some oncogene products are hematopoietic growth factors or growth factor receptors while others regulate cell proliferation or differentiation by diverse mechanisms. Disruption of the balance between these processes seems the most likely mechanism of oncogene related leukemogenesis. If the role of oncogenes in human leukemias can be defined, innovative diagnostic and therapeutic strategies may be forthcoming.
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PMID:Oncogenes and leukemia. 240 17


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