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)

We report analysis of allele-specific expression of N-RAS transcripts in myeloid leukaemic cells and cell lines. Expression was assessed by an assay of reverse-transcription/PCR combined with differential hybridization with mutation-specific oligonucleotides. In cells from all patients with acute myeloid leukaemia (AML) and in myeloid cell lines HL-60 and THP-1, expression of both the wild-type allele and the abnormal allele altered by a point mutation could be detected, albeit not always at comparable levels. This might be due for instance to allelic exclusion. The assay described provides a means of analysing the degree of expression of dominant oncogenes.
 ...
PMID:Detection of allele-specific expression of N-RAS oncogenes in human leukaemia cells. 139 Feb 9

Human granulocyte colony-stimulating factor (G-CSF) receptors on human acute leukemia cells were investigated using human G-CSF iodolabeled by the lactoperoxidase method. Among various human leukemic cell lines, only cells of myelogenous lineage including HL-60, THP-1 and U937 had one type of high-affinity receptor for G-CSF, as shown by Scatchard analysis. Fresh leukemia cells from 19 patients with acute myelogenous leukemia (AML) were then studied. Specific receptors for G-CSF were demonstrated on blast cells in all 19 cases, the mean number of G-CSF receptors per AML cell ranging from 95 to 1436. G-CSF receptors on AML cells appeared to be a single affinity type, although some variations were observed. The mean number of G-CSF receptors on leukemic cells from patients with either FAB M3 or FAB M2 was greater than that of cells from patients with M1 (p less than 0.01, p less than 0.10, respectively). Moreover, the mean number of receptors for G-CSF on CD13- and CD34-positive AML cells was higher than that on CD13-negative and CD34-positive AML cells (p less than 0.01), and the mean number of G-CSF receptors on CD7-positive AML cells was lower than that for CD7-negative AML cells (p less than 0.10). Since the FAB classification and surface phenotypes reflect maturation stages, our findings indicate that the distribution of G-CSF receptors, even on AML cells, may be related to the maturation process.
 ...
PMID:Human granulocyte colony-stimulating factor receptors in acute myelogenous leukemia. 170 27

Several new cytostatic drugs have entered clinical phase I-II studies for the treatment of leukemia: the most promising are pyrimidine analogs such as 5-aza-cytidine, 5-aza-2'-deoxycytidine, 5-aza-cytosine arabinoside, and 2',2'-difluorodeoxycytidine. Fludarabine, a fluorinated purine analog, appears to be active in CLL and multiple myeloma. Deoxycoformycin, an adenosine analog, showed good activity in the treatment of hairy cell leukemia and T-cell neoplasias. 2-chloro-deoxyadenosine has recently been introduced into the treatment of CLL and hairy-cell leukemia refractory to deoxycoformicin. Tiazofurin, an antimetabolite which interferes with nicotine-adenine-dinucleotide (NAD) metabolism, has been applied in CML blast crisis. Other agents include 13-cis retinoic acid and 1, 25-dihydroxy vitamin D3 as differentiation inducers, and homoharringtonine, an alkylating agent which is widely used for ANLL treatment in China. Among new anthracyclines, aclarubicin, idarubicin, THP-adriamycin and fluoro-adriamycin should be mentioned. Mitoxantrone, a substituted anthraquinone, has successfully been applied in the treatment of relapsed and refractory ANLL. Amsacrine (m-AMSA), finally, is a synthetic aminoacridine which intercalates into DNA and inhibits DNA topoisomerase II. m-AMSA is not cross-resistant to anthracyclines and has been particularly active in ANLL treatment. Studies using m-AMSA alone or in combination revealed comparable results to anthracycline--containing regimens. Cardiotoxicity of the anthracycline congestive type has not been observed with m-AMSA. The EORTC Leukemia Cooperative Group has successfully used m-AMSA in several trials prepositioning this drug stepwise: from relapsed and refractory ANLL, into intensive maintenance treatment during first remission in ANLL, and, still on-going, into intensive consolidation.
 ...
PMID:New drugs in the treatment of acute and chronic leukemia with some emphasis on m-AMSA. 206 23

Aclacinomycin is a member of naturally occurring anthracyclines having three sugar moieties in the molecule. It showed antitumour activity on various mouse and rat tumours. Combination therapy with AraC etc. gave remarkable clinical results on acute myeloid leukaemia. Aclacinomycin strongly inhibits RNA synthesis of the tumour cells. It has lower cardiac toxicity than adriamycin and no mutagenicity. THP-Adriamycin is a derivative of adriamycin designed from the structure of baumycins. It showed stronger effects than adriamycin in inhibiting many mouse tumours such as L1210 and P388 leukaemia, B16 melanoma and colon 38 adenocarcinoma. THP-Adriamycin is rapidly taken up by both adriamycin-sensitive and resistant leukaemic cells. Its level of cardiac toxicity is as low as that of aclacinomycin. Ditrisarubicins are new naturally occurring anthracyclines isolated from Streptomyces having six sugar moieties in the molecule. Ditrisarubicin has a potent cytostatic and antitumour activities on adriamycin resistant mouse leukaemia. Its binding constant to DNA is extremely high compared with other anthracyclines.
 ...
PMID:Experimental studies of new anthracyclines: aclacinomycin, THP-adriamycin and ditrisarubicins. 244 79

Several new cytostatic drugs have entered clinical Phase I-II studies for treatment of leukemia: most promising are pyrimidine analogues such as 5-Azacytosine arabinoside, 5-Aza-2-deoxycytidine, 5-Azacytidine, cyclocytidine, and 2'-2'-difluorodeoxycytidine. They act on different biochemical levels towards DNA-synthesis. Fludarabine is a purin analogue and seems very active in treating CLL. Tiazofurin is an antimetabolite counter-acting nicotinic acid with most promising activity in CML blast crisis. Other substances include deoxycoformycin, an adenosine analogue for treatment of T-cell neoplasias, 1, 25-dihydroxy vitamin D 3 as differentiation inducer, and homoharringtonine, an alkylating agent widely used for treating de novo AML in China. New anthracyclines are THP-adriamycin, fluoroadriamycin, and 4-demethoxydaunorubicin. Amsacrine (mAMSA) finally, is a synthetic aminoacridine with DNA-intercalating properties. The intact acridine ring appears essential for antitumor activity. The plasma clearance of both total amsacrine and unchanged parent species is biphasic. There is a considerable influence of hepatic and renal impairment on plasma clearance. Clinical toxicities include marked myelosuppression, gastrointestinal symptomes, phlebitis, mucocutaneous lesions, occasionally alopecia and neurotoxities. It is a very active drug, particularly in treating AML. Studies using mAMSA alone or in combination revealed comparable results to the anthracyclines. The E.O.R.T.C. Leukemia Cooperative Group has used successfully mAMSA in several trials: relapsed and refractory AML, intensive maintenance treatment during first remission in AML, and, still on-going, during intensive consolidation randomized against BMT in AML-patients under the age of 45 years, and randomized against standard consolidation between the age of 45 and 60 years.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:New drugs in the treatment of acute and chronic leukaemia: current role of mAMSA. 269 2

The regulation of IgG Fc receptor (Fc gamma R) expression by retinoic acid (RA) in human myelomonocytic cells at different stages of maturation was studied. RA suppressed IgG-coated erythrocyte (EA) rosette formation of myelomonocytic cells blocked at relatively late stages of differentiation such as ML-1, U-937, THP-1-T, normal monocytes, and fresh cells of patients with acute myelomonocytic leukemia. However, RA increased the percentage of EA rosetting promyelocytes of HL-60 and of patients with acute promyelocytic leukemia and a part of myeloblasts isolated from acute myelogenous leukemia patients. Other myeloblasts including KG-1a, KG-1, and fresh cells from patients with acute myelogenous leukemia were not affected. A kinetic study using HL-60 and THP-1-T demonstrated that an increase required at least a 48-h exposure and that the maximum decrease required approximately 6 h. The RA effect on both cell lines was dose-dependent. The number of Fc gamma R of HL-60 and THP-1-T treated with RA became very close, although untreated THP-1 had almost 10 times as many as HL-60. Kd for IgG in both THP-1-T and HL-60, either untreated or treated with RA, remained unchanged. These observations indicate that one of the important roles of RA is regulation of Fc gamma R expression in myeloid cells.
 ...
PMID:Retinoic acid regulates IgG Fc receptor expression in human myelomonocytic leukemia cells and normal peripheral monocytes. 297 58

DNA transfection analyses using the tumorigenicity assay were performed on seven human acute myelocytic leukemia (AML) cell lines. DNAs from all cell lines induced tumors in nude mice. Respective transforming sequences could be identified as activated N-ras genes in AML cell lines THP-1, KG-1 and Rc2a. We observed the transfer of five putative novel transforming sequences from DNAs of cell lines U937, ML-1, HEL and CTV-2. These sequences appear to be unrelated to each other and previously known oncogenes. Transfections containing these transforming genes show distinctive biological and morphological characteristics. Our data suggest that the transforming sequences reported here became activated during the transfection process rather than the AML cell line.
 ...
PMID:Novel transforming sequences in human acute myelocytic leukemia cell lines. 332 81

Impaired polyglutamylation of methotrexate (MTX) and thus poor retention is believed to be the basis of intrinsic resistance in blasts from patients with acute myeloid leukemia (AML) to MTX. We studied additional samples from patients with this disease, and confirmed that polyglutamylation of MTX was poor in ANLL blast cells. However, in one subset of ANLL, acute monocytic leukemia, (M5) leukemia blasts were found to be capable of accumulating and forming long-chain MTX polyglutamates. An acute monocytic leukemia cell line, THP-1 also was found to accumulate high levels of MTX polyglutamates and was relatively sensitive to MTX, strengthening the concept that M5 blasts may be sensitive to this drug. MTX may be an overlooked drug for the treatment of acute monocytic leukemia.
 ...
PMID:Acute monocytic leukemia: a myeloid leukemia subset that may be sensitive to methotrexate. 753 68

Microspectrofluorometry allows the analysis of fluorescent molecules such as anthracyclines in the nucleus of isolated living cells. Using this technique, we confirmed that the amount of doxorubicin or THP-doxorubicin incorporated into the nucleus was related to the resistant or sensitive character of K562 cells. It was then extended to the study of fresh leukemic cells and kinetic studies were performed allowing the calculation of the retention rate (RR) of anthracycline (THP-doxorubicin) into the cell nucleus. A reproducibility study confirmed the accuracy of the method. Blast cells collected in patients with acute myeloid (n = 22) or lymphoid (n = 8) leukemia, at diagnosis (n = 26), or in relapse (n = 4) have been studied. RR varied from 8 to 98% independently of the type of leukemia or the clinical status. RR did not correlate either with P-glycoprotein or with CD34 expression although this latter result should be confirmed on a higher number of subjects. Among 18 patients presenting with AML at diagnosis, 14 have been treated with intensive chemotherapy including anthracyclines; the only one who had resistant disease had the lowest RR value. In conclusion, the results obtained here show that microspectrofluorometry allows the performance of kinetic studies on fresh leukemic cells in order to quantify chemo-resistance phenomena related to drug transport.
 ...
PMID:In vitro study of THP-doxorubicin retention in human leukemic cells using confocal laser microspectrofluorometry. 764 25

Human monocytes are involved in host defense against neoplastic cells. In view of cellular immunotherapy with cytotoxic monocytes in minimal residual disease of acute myeloid leukemia we have studied the role of monocytes in cell cycle dependent leukemic cell death of U937, THP-1, and HL-60 cells in vitro. Leukemic cells separated in G1 of the cell cycle by countercurrent centrifugal elutriation were highly susceptible to monocyte mediated cytotoxicity, whereas cells in S and G2-M were less sensitive or completely resistant as compared to unfractionated control cells. HL-60 cells resistant to cytotoxic monocytes became sensitive to monocyte mediated cytotoxicity upon differentiation induction with 1,25-dihydroxyvitamin D3 which paralleled an accumulation of cells in G1 of the cell cycle. The differences in susceptibility of cell phase separated populations to monocyte mediated cytotoxicity paralleled differences in sensitivity to the cytotoxic effects of tumor necrosis factor alpha, as secreted by gamma-interferon activated monocytes. Furthermore, monocyte mediated cytotoxicity was markedly inhibited in the presence of anti-CD11/CD18 monoclonal antibodies recognizing the alpha and beta chains of the beta 2-integrin adhesion proteins. By fluorescence activated cell sorter immunofluorescence a marked increase in mean fluorescence density of the beta 2-integrins could be demonstrated on cells in G1 of the cell cycle as compared to unseparated leukemic cells. A decrease in mean fluorescence density was shown for cells in G2-M. By blocking experiments with anti-CD11/CD18 monoclonal antibodies, the differences in mean fluorescence density were functionally relevant since cells in G1 were shown to be the most sensitive cells to beta 2-integrin dependent monocyte mediated cytotoxicity. In conclusion these data show that differences in sensitivity to tumor necrosis factor and in the expression of beta 2-integrins may play a central role in cell cycle dependent monocyte mediated antileukemic activity.
 ...
PMID:Cell cycle specific effects of tumor necrosis factor alpha in monocyte mediated leukemic cell death and the role of beta 2-integrins. 768 34


1 2 3 4 5 6 7 8 9 10 Next >>