Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since 1971, 8,483 women with primary breast cancer participated in seven trials evaluating adjuvant chemotherapy. Leukemia occurred in only three of 2,068 patients treated by operation alone. The cumulative risk was 0.06% after 10 years in those free of metastases or a second primary tumor, and 0.27% in those with tumor. Thus, leukemia is not an important factor in the natural history of breast cancer. Five of 646 women receiving postoperative regional radiation developed leukemia, an overall risk of 1.39 +/- .49% at 10 years. Twenty-seven cases of leukemia (0.5%) and seven of myeloproliferative syndrome (0.1%) were recorded in 5,299 patients who received L-phenylalanine mustard (L-PAM)-containing regimens. The maximum cumulative risk of leukemia in chemotherapy recipients (leukemia of any type and myeloproliferative syndrome) was 1.68 +/- .33% at 10 years following operation. The risk excluding those with myeloproliferative syndrome was 1.29 +/- .28%. The risk of leukemia in patients free of metastases or a second primary was 1.11 +/- .30% at 10 years, and when combined with myeloproliferative syndrome, it was 1.54 +/- .36%; risks not significantly greater than observed following radiation (P = .58 and .29). No cases of leukemia were observed during the 2 years of chemotherapy and none have occurred after the seventh postoperative year. Comparisons with the surveillance, epidemiology, and end results tumor registries (SEER) data indicate an increased relative risk of acute myelogenous leukemia following postoperative regional radiation (P less than .01) and adjuvant chemotherapy (P less than .001). The findings indicate that hematologic disorders are side effects of both radiation and alkylating agents used in the adjuvant treatment of primary breast cancer. The risk of such events is lower than that reported following treatment of other solid tumors and hematologic malignancies by chemotherapy. The benefit from adjuvant chemotherapy for breast cancer exceeds the risk of leukemia. Since chemotherapy is not uniformly beneficial, efforts should be directed toward identifying responders so that only those who will benefit are exposed to the risk.
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PMID:Leukemia in breast cancer patients following adjuvant chemotherapy or postoperative radiation: the NSABP experience. 390 49

The mechanism of alkylating agent-induced leukemia is unknown. For the determination of whether chronic alkylating agent treatment of hematopoietic stem cells in vitro was detectably leukemogenic, murine long-term bone marrow cultures (LTBMC) and clonal interleukin 3 (IL-3)-dependent multipotential hematopoietic progenitor cell lines [B6SUtA clone (cl) 27 and Ro cl 3-1] derived from LTBMC were chronically pulse treated in vitro with the alkylating agent melphalan [L-phenylalanine mustard (L-PAM)]. Weekly treatment of C3H/HeJ or CD-1 Swiss mouse LTBMC with 3 X 10(-6)M L-PAM significantly decreased cumulative production of nonadherent granulocytes and granulocyte-macrophage progenitor cells responsive to L-cell or WEH1-3 cell colony-stimulating factor compared to the production seen in untreated control cultures; it also significantly reduced the hematopoietic longevity (13 wk compared to greater than 20 wk for untreated control cultures). Weekly, twice weekly, or daily (3 X 10(-6)M) L-PAM treatment of IL-3-dependent cell lines induced gradual L-PAM adaptation in the absence of a detectable change in the maximum binding capacity of 125I-labeled IL-3. No leukemogenic variants of line B6SUtA cl 27 were detectably induced. However, 3 stably expressed marker chromosomes were induced after 12 months of L-PAM treatment of line B6SUtA cl 27. Thus IL-3-dependent hematopoietic progenitor cells slowly adapt to L-PAM when in suspension culture in vitro. Physiologic expression of drug toxicity in LTBMC may prevent this hematopoietic cell gradual adaptation.
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PMID:Biologic effects of prolonged melphalan treatment of murine long-term bone marrow cultures and interleukin 3-dependent hematopoietic progenitor cell lines. 391 12

PTT.119 [p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met ethoxy HCl], a new synthetic tripeptide, was highly effective against the L-phenylalanine mustard (L-PAM) resistant (L1210/L-PAM and P388/L-PAM) tumor lines, as well as the sensitive L1210 leukemia. Cytolytic activity of PTT.119 against all three leukemias was significantly greater than equimolar doses of L-PAM. These in vitro results paralleled the significant increases in mean survival times of hosts and, in some cases, abrogations of tumor formation observed in the in vivo bioassays of PTT.119-treated L1210 and L1210/L-PAM cells. Dose-response studies failed to demonstrate cross-resistance to the tripeptide by L-PAM resistant cells. Doses of PTT.119 required to reduce the viable fraction by 50% (tissue culture dose 50, TCD50) or 100% (TCD100) were 1.3- to 3-fold lower for the L-PAM resistant cells than for the L1210 leukemia. In comparison, L-PAM was unable to completely eliminate cell survival; 0.2 to 3% of the cells in all three leukemias remained viable even at doses of 75 and 163 microM. In similar studies, L1210 leukemia cells made resistant to methotrexate (L1210 MTX) and cisplatin (L1210DDP) were also completely susceptible to PTT.119; TCD50 values of the two resistant lines were 1.94 microM for L1210 MTX and 0.525 microM for L1210DDP compared to 2.38 microM for the susceptible parent L1210S leukemia. Continuous low-dose PTT.119 treatment of MJY-alpha mammary tumor cells for 8 months and exposure of L1210 leukemia to escalating levels of tripeptide for over 100 passages failed to select or induce drug-resistant phenotypes in either cell line. PTT.119 appears to be a poor mutagen and is unlikely to readily increase the probability of drug-resistant mutants in the tumor cell populations.
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PMID:PTT.119, p-F-Phe-m-bis-(2-chloroethyl)amino-L-Phe-Met ethoxy HCl, a new chemotherapeutic agent active against drug-resistant tumor cell lines. 404 Mar 66

1. Substance P (SP) induces histamine release from isolated rat peritoneal mast cells at concentrations of 0.1-10 muM.2. Inhibitors of glycolysis and oxidative phosphorylation prevent the release of histamine induced by SP.3. Cells heated to 47 degrees C for 20 min release histamine when treated with an agent causing cell lysis but fail to release in response to SP.4. SP does not release histamine by interacting with cell-bound IgE.5. Histamine release by SP is rapid, with more than 90% of the response occurring within 1 min of the addition of the peptide to mast cells at 37 degrees C.6. Substance P, unlike antigen-antibody or compound 48/80, does not show enhanced release of histamine when calcium (0.1-1 mM) is present in the extracellular medium but calcium increases the response to SP when the ion is added after the peptide. Extracellular calcium (0.1-1 mM), magnesium (1-10 mM) and cobalt (0.01-0.1 mM) all inhibit SP-induced histamine release when added before the peptide. Pre-treatment of the cells with EDTA (10 mM) and washing in calcium-free medium inhibits the histamine release induced by SP.7. Histamine release induced by SP was optimum at an extracellular pH of 7.2.8. A number of peptides structurally related to SP were examined for histamine-releasing activity. At the concentrations tested, the N-terminal dipeptides Lys-Pro and Arg-Pro, tuftsin, physalaemin, eledoisin, SP(3-11), SP(4-11) and [p-Glu(6), p-amino Phe(7)]-SP(6-11) were all found to be inactive. The relative activities of the other peptides were: [Formula: see text]9. Rat basophilic leukaemia cells (RBL-2H3) fail to respond to SP at concentrations which activate rat mast cells. Release of 5-hydroxytryptamine by immunological activation of RBL cells is not changed by the presence of SP.10. The mechanism of action of SP on mast cells and the nature of the SP receptor on mast cells is discussed in relation to SP receptors in other cell types.
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PMID:The effects of substance P on histamine and 5-hydroxytryptamine release in the rat. 618 68

The production of stable T-cell clones is essential for the study of T-cell-derived, specific immunoregulatory products and of specific T-cell receptors. T-cell clones have been established by radiation leukaemia virus (RadLV)-induced transformation of suppressor T lymphocytes specific for hen egg white lysozyme (HEL). We report here that culture supernatant obtained from these T-cell clones can, when injected into mice, specifically suppress the anti-HEL antibody response. This monoclonal T-cell product suppresses the antibody response induced by HEL and human lysozyme, but not that induced by ring-necked pheasant egg white lysozyme (REL), thus displaying fine antigenic specificity probably restricted to an epitope involving phenylalanine at amino acid residue 3, present in the N-terminal region of HEL and shared by human lysozyme but absent in REL. The suppression induced by this monoclonal T-cell product is restricted by both H-2 and Igh-1 genes whereas anti-HEL antibodies bearing a predominant idiotype are induced in all mice strains tested, irrespective of their H-2 haplotype or Igh-1 allotype.
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PMID:Monoclonal suppressor T-cell factor displaying V H restriction and fine antigenic specificity. 619 92

The alterations of stimulus-induced membrane potential changes, superoxide (O2-)-producing capacity and phagocytic activity during differentiation of human granulocytes were investigated in the human leukemia cell lines HL-60 and KG-1 differentiating in vitro and in human leukemic granulocytes obtained from chronic myelogenous leukemia patients. HL-60 cells incubated with dimethyl sulfoxide or with retinoic acid showed progressively increasing O2- production as well as membrane potential changes (depolarization) on contact with phorbol myristate acetate or the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine, with a concomitant increase in the proportion of mature cells of the granulocytic type. Phagocytosis of latex particles, yeast, and oil droplets appeared 24 h after incubation with dimethyl sulfoxide and anteceded the increment of O2- production and membrane potential changes, both of which appeared concomitantly 3 d after incubation with dimethyl sulfoxide. Similar findings were observed when immature and mature granulocytes obtained from chronic myelogenous leukemia patients were stimulated by phorbol ester, the chemotactic peptide, or calcium ionophore A23187, and the amount of O2- production was parallel to the magnitude of membrane potential changes. HL-60 and KG-1 cells incubated for 1-6 d with phorbol myristate acetate showed neither O2- production nor membrane potential changes on contact with phorbol ester, chemotactic peptide, or A23187, although such cells resembled macrophages morphologically, and their phagocytic activity was significantly increased. O2- production and membrane potential changes in normal granulocytes induced by phorbol ester, chemotactic peptide and A23187 were inhibited by 2-deoxyglucose. These findings indicate that the O2--producing system and the system provoking membrane potential changes may develop concomitantly as human granulocytes mature and differentiate, and that the development of these systems and of phagocytic activity may be independently regulated.
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PMID:Functional maturation of membrane potential changes and superoxide-producing capacity during differentiation of human granulocytes. 620 May 1

Alkaline phosphatase was studied in cell lines established from Radiation Leukemia Virus induced thymic lymphomas of C57BL/Ka mice. The cytochemical staining techniques and flow cytofluorimetry analysis described by Dolbeare et al. (J. Histochem. Cytochem., 1980, 28, 419-426) were used. The alkaline phosphatase found in lymphoma cells was heat labile and L-homoarginine. L-phenylalanine and p-bromotetramisole sensitive and is probably similar to the isoenzyme present in mouse placenta, kidney and liver. Very little alkaline phosphatase activity was detected in normal thymus of adult mice, suggesting that the method used in the paper could be helpful for studying the emergence of the first neoplastic cells during the leukemogenic process.
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PMID:[Cytochemical detection and cytofluorimetric analysis of alkaline phosphatase in continuous lines of thymic lymphomas induced in mice by a radiation leukemia virus]. 629 66

The human HL-60 myeloid leukaemia cell line developed, during maturational changes induced by dimethyl sulphoxide, an enhanced capacity for phorbol myristate acetate- stimulated oxidative activity and acquired a cytochrome b. Titration of the absorbance at 559 nm at potentials of-190 to -370 mV indicated that this cytochrome had a very low potential, differentiating it from mitochondrial and endoplasmic reticulum cytochromes and identifying it as the cytochrome b(-245) that has been recently found in other phagocytic cells. Subcellular fractionation studies of mature HL-60 cells showed that cytochrome b had a dual distribution within the cell. The lighter peak of activity was associated with the plasma membrane markers, adenylate cyclase and receptors for the N- formal-L-methionyl-L-leucyl-L-phenylalanine (f-Met-Leu-Phe) peptide. The denser components localized with the mitochondria but were distinct from mitochondrial cytochromes because whereas the activity of cytochrome c oxidase fell during HL-60 cell maturation, that of this cytochrome b was markedly increased. Concentrations of myeloperoxidase were unrelated to activity of the oxidase system and decreased as the cell matured. The increase in the concentrations of cytochrome b with cellular maturation parallelled the increase in the stimulated nonmitochondrial respiratory activity of these cells. The turnover of the hexose monophosphate shunt of immature cells was increased by the oxidising agents, methylene blue and tert-butylhydroperoxide, indicating that these immature cells have stimulated nonmitochondrial respiratory activity by maturing HL-60 cells is associated with, and is probably dependent upon, the acquisition by these cells of the cytochrome b(-245) oxidase system.
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PMID:Development of cytochrome b and an active oxidase system in association with maturation of a human promyelocytic (HL-60) cell line. 629 56

We have determined the nucleotide sequences of long terminal repeat (LTR) regions of Syrian hamster intracisternal A particle (IAP) genes. The size of the LTRs was 350 base-pairs (bp) and 376 bp in two clones, H10 and H18, respectively. Two LTRs at both ends of the IAP gene were linked to directly repeating 6 bp hamster sequences. Many structural features common to the integrated retroviral LTRs such as "CAT" box, "TATAA" box, polyadenylation signal, and terminal inverted repeat (3 bp), were present on each LTR. The estimated length of R region (about 60 bp) was similar to that of the murine leukemia-sarcoma virus. In contrast, the calculated U5 region of 54 bp was the shortest among those of the retroviruses so far studied. Furthermore, from the analysis of primer binding sites, phenylalanine tRNA was for the first time identified as a presumed primer tRNA for reverse transcription. These results clearly distinguish Syrian hamster IAP LTRs from other retroviral ones. Based on the comparison of the sequences between Syrian hamster and laboratory mouse LTRs, the structural features peculiar to the IAP LTRs and the origin of the IAP genes are discussed.
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PMID:Long terminal repeat sequences of intracisternal A particle genes in the Syrian hamster genome: identification of tRNAPhe as a putative primer tRNA. 631 80

Permeabilised, dimethyl sulphoxide-differentiated HL-60 human myelomonocytic leukemia cells accumulate 45Ca in an ATP-dependent manner. The 45Ca is taken up by a pool thought to be a component of the endoplasmic reticulum. Inositol trisphosphate induced a rapid release of Ca from this pool, suggesting that this molecule which is formed in these cells in response to f-Met-Leu-Phe may play a role in agonist-induced Ca metabolism.
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PMID:Inositol 1,4,5-trisphosphate may be a signal for f-Met-Leu-Phe-induced intracellular Ca mobilisation in human leucocytes (HL-60 cells). 633 56


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