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)

Serum ferritin concentration was studied in 136 patients with different types of acute leukemia. Pretreatment serum ferritin concentrations in the immature myeloblastic leukemia (M1 and M2 of the FAB-classification of acute leukemias) was found to be highly increased compared to the more mature types of acute myeloblastic leukemias (M3 to M5) and the acute lymphoblastic leukemias (L1 to L3). Investigation of the intracellular ferritin concentration showed, that the serum ferritin levels paralleled the intracellular ferritin concentration within the leukemic blasts. Within the immature myeloic blasts (M1) the intracellular ferritin concentration was 14-fold increased compared to normal granulocytes. This correlated with the 17-fold increased serum ferritin levels in these patients. Intracellular ferritin concentrations within the leukemic blasts of more mature types of acute leukemia (M3 to M5) were found to be only slightly increased. These data support the concept, that an increased synthesis and release of ferritin by the leukemic blasts is responsible for the increased serum ferritin concentration. This concept is also supported by the observation, that a further increase of serum ferritin concentration was seen during a cytotoxic chemotherapy. It is noteworthy, that this increase was more pronounced in the immature leukemias obviously caused by a loss of intracellular ferritin from the damaged leukemic blasts. The serum ferritin levels followed closely the activity of the disease. Increased pretreatment serum ferritin concentrations normalized completely when patients achieved complete remission. In contrast, in patients with tumor relapse or tumor progression serum ferritin concentrations increased again. These data suggest that the serum ferritin in immature myeloblastic leukemia has the characteristics of a tumor associated marker.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Ferritin in acute leukemia. Serum ferritin concentration as a nonspecific tumor marker for M1 and M2 myeloid leukemia]. 188 10

It has been suggested that circulating immune complexes (CIC) favor tumor progression by suppressing the host's immune response to malignant cells via blocking factors to cell-mediated cytotoxicity. We prospectively measured CIC by the C1q binding assay in 100 untreated patients with acute myeloid leukemia (AML) de novo. The median CIC level was 135, the range 0-1000, and the mean +/- standard error (SE) 175 +/- 18 micrograms/ml. Sixty-eight patients, termed abnormal, had C1q binding levels greater than 2SE above the mean of the normal population (61 +/- 15 micrograms/ml). There were no significant differences between the 32 patients with normal CIC and the 68 with abnormally elevated CIC in any pretreatment characteristic: gender, age, white blood cell count (WBC), platelets, leukemia cell mass, LDH, immunoglobulins, or fibrinogen. Abnormal CIC levels did not correlate with FAB morphology, the presence of a clonal chromosomal abnormality (76% of all patients), or with specific cytogenetic subgroups, although nine of 11 patients with acute promyelocytic leukemia and t(15;17) had abnormal CIC. There were no significant differences in complete remission (CR) rates after the first chemotherapy course (45 vs 40% for normal vs abnormal CIC) or after all courses of treatment (55 vs 65%). Survival from diagnosis was not significantly different for the normal and abnormal groups (9.3 vs 5.8 months, p = 0.24), but survival after achieving a CR was markedly longer for those with normal pretreatment CIC (33.8 vs 11.7 months, p = 0.0068). Pretreatment CIC strongly correlated with remission duration for the 59 patients who achieved CR (16.5 months for 17 normal patients vs 6.9 months for 42 abnormal patients, p = 0.0002). This was independent of age, WBC, leukemia cell mass, or FAB morphology. Within the lowest C1q quartile (less than 60 micrograms/ml), 43% of the patients have not relapsed with a minimum follow-up of 18 months compared to only 6-14% for the three higher quartiles. We conclude that host immunity as assessed by CIC levels has little effect on the initial response to therapy but may play a role in maintaining remission in AML.
Leukemia 1991 Feb
PMID:Circulating immune complexes correlate with remission duration in acute myeloid leukemia. 202 Jan 95

Two sublines of the human T-lymphoblast leukemia cell line CCRF-CEM, which were resistant to methotrexate (MTX) due to defective MTX polyglutamate synthesis, were karyologically characterized. No statistically significant differences in the modal number of chromosomes were noted in resistant cells (CCRF-CEM/P) as compared to parent cells (91, range, 86-123; and 93, range; 78-103, respectively). Fifteen marker chromosomes were identified and their origins at least partially established. An isochromosome 7q, (marker 13) was present in all MTX-resistant cells but was not found in any sensitive cell karyotype. This marker chromosome may be involved in the emergence of drug-resistant cells from the parental population of CCRF-CEM cells. In all cell lines, chromosomes 8, 9 and 14 appear to be highly unstable and are involved in the genesis of many marker chromosomes. These chromosomes are also implicated in the in vivo genesis of various leukemias and lymphomas, which suggests that both in vivo tumor progression and in vitro cellular adaptation are marked by chromosome mutations that may activate multiple oncogenes.
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PMID:Chromosomal characterization of methotrexate-resistant human T-lymphoblast leukemia cells (CCRF-CEM) with impaired polyglutamylation. 204 34

Structure-activity studies with nine glycol alkyl ethers were conducted with a cellular leukemia transplant model in male Fischer rats. This in vivo assay measures the effects of chemical treatment on neoplastic progression in transplant recipients. Chemicals were given ad libitum in the drinking water simultaneously with the transplants and continued throughout the study. In all, 20 million leukemic cells were injected s.c. into syngeneic rats, which after 60 days resulted in a 10-fold increase in relative spleen weights, a 100-fold increase in white blood cell counts, and a 50% reduction in red blood cell (RBC) indices and platelet counts. At this interval, ethylene glycol monomethyl ether (2-ME) given at a dose of 2.5 mg/ml in the drinking water completely eliminated all clinical, morphological, and histopathological evidence of leukemia, whereas the same dose of ethylene glycol monoethyl ether (2-EE) reduced these responses by about 50%. Seven of the glycol ethers were ineffective as anti-leukemic agents, including ethylene glycol, the monopropyl, monobutyl, and monophenyl ethylene glycol ethers, diethylene glycol, and the monomethyl and monoethyl diethylene glycol ethers. 2-ME more than doubled the latency period of leukemia expression and extended survival for at least 210 days. A minimal effective dose for a 50% reduction in the leukemic responses was 0.25 mg/ml 2-ME in the drinking water (15 mg/kg body weight), whereas a 10-fold higher dose of 2-EE was required for equivalent antileukemic activity. In addition, the in vitro exposure of a leukemic spleen mononuclear cell culture to 2-ME caused a dose- and time-dependent reduction in the number of leukemia cells after a single exposure to 1-100 microM concentrations, whereas the 2-ME metabolite, 2-methoxyacetic acid, was only half as effective. The two glycol alkyl ethers with demonstrable anti-leukemic activity, 2-ME and 2-EE, also exhibited a favorable efficacy-to-toxicity ratio and should be considered for further development as chemotherapeutic agents.
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PMID:The chemotherapeutic potential of glycol alkyl ethers: structure-activity studies of nine compounds in a Fischer-rat leukemia transplant model. 235 63

T-cell lymphomas induced in rats by Moloney murine leukemia virus acquire increasing numbers of proviruses in their genome during tumor progression in vivo and passage of tumor cells in vitro. To determine whether the proviruses progressively acquired during tumor progression play a causal role in this process, we cloned one of them from a cell line derived from the primary tumor 2772. A probe from the cellular DNA flanking the provirus was used to analyze 79 DNA samples from primary tumor tissues of 28 tumor-bearing rats and 80 DNA samples from 30 independent tumor cell lines. This analysis revealed a rearrangement in this region in the primary tumor derived from the thymus of one animal but not in a clone of the same tumor segregating in the spleen. Of the cell line DNA samples, three carried a provirus in this region. Two of these integration events had occurred independently in two clonally related sublines derived from tumor 2772, and they were followed by rapid selection in culture. On the basis of these findings this locus was named Tpl-1 (tumor progression locus 1). The Tpl-1 locus was mapped to rat chromosome 8 and to mouse chromosome 9 at a genetic distance of 1.2 +/- 0.9 centimorgans from the Ets-1 protooncogene. Although the genetic distance between Tpl-1 and Ets-1 indicates that they are different genes, analysis of Tpl-1 cDNA clones revealed that the two are closely related.
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PMID:Provirus insertion in Tpl-1, an Ets-1-related oncogene, is associated with tumor progression in Moloney murine leukemia virus-induced rat thymic lymphomas. 255 46

The incidence of the lethal growth of 10(1) L1210 murine leukemia cells in mice was higher in intraperitoneal (i.p.) (97%) than in intradermal (i.d.) (17%) inoculation, and survival time of mice was shorter in i.p. than i.d. inoculation. It was supposed that resident peritoneal cells (PC) enhanced tumor progression. I.d. inoculation of 10(1) L1210 cells mixed with 10(6) PC induced a lethal tumor growth at higher incidence than that of 10(1) L1210 cells alone or the mixture of 10(1) L1210 cells and 10(4) peripheral blood mononuclear cells (PBM) did. Furthermore, co-inoculation of a tumorigenic number of L1210 cells (10(3] with 10(6) PC resulted in marked shortening of median survival time of mice. Similar growth enhancing effect of PC was observed in Meth 1 fibrosarcoma. Meth A fibrosarcoma and colon carcinoma 26 (C26). Further study showed that PC, intact or X-rayed, helped the in vitro tumor growth under the conditions in which L1210 alone did not grow at all, whereas PBM had no enhancing effect to L1210 growth. We characterized the cells involved in tumor growth enhancement by the in vivo and in vitro tests. Plastic dish adherent cells of PC which were Mac-1 positive, large in size and resistant to X-ray, enhanced L1210 growth, whereas non-adherent cells which were Mac-1 negative and small in size, did not. These data suggest that the cells responsible for enhancing activity of tumor progression in the peritoneal cavity were macrophages (M phi).
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PMID:Environmental conditions favorable for tumor progression in peritoneal cavity induced by peritoneal cells without tumor selectivity. 268 89

We have compared proviral integrations near (putative) proto-oncogenes in Moloney murine leukemia virus-induced primary and transplanted T cell lymphomas. We previously found proviruses integrated near c-myc, pim-1, and N-myc in primary tumors (Selten et al., 1984; Van Lohuizen et al., 1989a; Van Lohuizen et al., 1989b). We have now identified an additional common proviral integration site, called pim-2, that carries somatically acquired proviruses in the majority of transplanted tumors. In primary tumors integration near pim-2 is usually undetectable or present in only a minor fraction of the tumor cells. This subpopulation selectively grows out upon transplantation. Insertion near pim-2 is a relatively late event in tumorigenesis and is often preceded by proviral insertions in other common insertion sites, yielding tumor clones which carry proviruses in up to three different common insertion sites within the same cell (c-myc, pim-1 and pim-2). The data suggest that pim-2 plays an important role in tumor progression.
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PMID:Evidence for the involvement of pim-2, a new common proviral insertion site, in progression of lymphomas. 272

The efficacy of a leukemia cell transplant model to measure potential chemotherapeutic activity was tested with five different chemicals that had previously been evaluated in 2-year studies. Leukemic spleen cells from Fischer rats were injected subcutaneously into syngeneic recipients and the effects of chemical treatment on tumor progression were evaluated at 70 days post-transplant. The data from the short-term assay were in all cases correlated with the trends reported for mononuclear cell leukemia in 2-year studies, where two chemicals were reported to decrease the incidence and three chemicals were reported to increase the incidence of leukemia. Short-term treatment with the two chemicals which caused negative trends for leukemia (2-ethoxyethanol or ethylene glycol monoethyl ether; 4-hexylresorcinol) delayed and/or reduced tumor growth in the transplant model in a dose-related fashion, as exhibited by reduction or elimination of splenomegaly and leukoblastosis, and a reversal in the depression of red blood cell indices or platelet counts. By contrast, the rate of tumor progression was increased in the short-term assay of the three chemicals which previously caused increased trends for leukemia in 2-year studies (pyridine; 2,4,6-trichlorophenol, dichlorvos). The severity of the mononuclear cell leukemia in the transplant recipients, as measured by histopathological examination of spleen and liver, was correlated with the changes in tumor growth rates. The in vivo leukemia transplant model is a short-term assay that could be used to screen a variety of potential chemotherapeutic agents, or to study structure-activity relationships within one class of chemicals.
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PMID:Development and validation of a cellular transplant model for leukemia in Fischer rats: a short-term assay for potential anti-leukemic chemicals. 279 89

Expression of several thymocyte surface antigens was monitored in a murine model system of thymic lymphoma induction in two different strains of mice. RF/J mice are sensitive to tumor induction by N-nitrosomethylurea (NMU) and by gamma-irradiation, while 129/J mice form tumors only upon NMU treatment. Latency periods for tumor formation were characteristically different depending upon the inducing agent and the mouse strain. We observed differences in thymic leukemia antigen and H-2K expression according to the mode of tumor induction and in relation to the mouse strain, implying multiple factors involved in target cell selection and tumor progression.
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PMID:Differential expression of surface markers on thymic lymphomas induced by two carcinogenic agents in different mouse strains. 288 44

We have reviewed literature data on 6,306 cases of hematological neoplasia--acute and chronic lymphatic and myeloid leukemias (CML excepted), myelodysplastic and chronic lymphoproliferative and myeloproliferative disorders, and malignant lymphomas--with the goal of quantitatively ascertaining how often cytogenetically unrelated clones occur in these diseases. Unexpectedly wide variations were found: in ANLL, unrelated clones were present in 1.1% of the 2,506 known cases with chromosome abnormalities characterized with banding technique; in the various myelodysplastic (MDS) and chronic myeloproliferative (CMD) disorders (total number of cases 1,299) the frequency was 4.3% and in lymphatic malignancies 1.3% (total case number 2,501). In the latter group the proportions varied between 0.4% and 0.6% in ALL and malignant lymphoma (ML) to as much as 6.2% in CLD and 7.3% in CLL. Some karyotypic abnormalities were encountered more often than would be expected from their general frequency in the various diseases. This discrepancy was particularly evident in MDS and CMD, where 5q- was found in slightly less and +8 in somewhat more than half of the 56 cases. Furthermore, these two aberrations were found as the only changes in the two coexisting clones in one-fourth of the material. Although if viewed in isolation these data would undoubtedly be best explained by assuming a multicellular origin of the neoplasm, it is entirely possible that what are cytogenetically perceived as unrelated clones could be subclones with some invisible aberration in common. If so, this interpretation indicates that changes like +8 and 5q-, both of which are common rearrangements in bone marrow neoplasms, are actually secondary changes that develop during tumor progression.
Leukemia 1989 Jan
PMID:Cytogenetically unrelated clones in hematological neoplasms. 290 9


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