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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hochberg and co-workers have predicted that an increase in host adult mortality due to parasites is balanced by an earlier age at first reproduction. In polygynous species we hypothesize that such a pattern would lead to diverging selection pressure on body size between sexes and increased sexual size dimorphism. In polygynous mammals, male body size is considered to be an important factor for reproductive success. Thus, under the pressure of a virulent infection, males should be selected for rapid growth and/or higher body size to be able to compete successfully as soon as possible with opponents. In contrast, under the same selection pressure, females should be selected for lighter adult body size or rapid growth to reach sexual maturity earlier. We investigated this hypothesis in the domestic cat Felis catus. Orange cats have greater body size dimorphism than non-orange cats. Orange females are lighter than non-orange females, and orange males are heavier than non-orange males. Here, we report the extent to which orange and non-orange individuals differ in infection prevelance for two retroviruses, feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV). FIV is thought to be transmitted almost exclusively through aggressive contacts between individuals, whereas FeLV transmission occurs mainly through social contacts. The pattern of infection of both diseases is consistent with the higher aggressiveness of orange cats. In both sexes, orange cats are significantly more infected by FIV, and tend to be less infected by FeLV than other cats. The pattern of infection is also consistent with an earlier age at first reproduction in orange than in non-orange cats, at least for females. These results suggest that microparasitism may have played an important role in the evolution of sexual size dimorphism of domestic cats.
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PMID:Retroviruses and sexual size dimorphism in domestic cats (Felis catus L.). 949 4

Controversy regarding the use of ad libitum feeding in chronic rodent toxicity studies will soon result in issue of a FDA Points to Consider document. Caloric intakes are now recognized to be important uncontrolled variables in bioassays because rodents chronically fed ad libitum become obese, reproductively senile and have increased incidences of age-related diseases, higher tumor burdens and decreased survival. The available literature suggests that ad libitum feeding neither optimizes the health and well-being of rodents nor provides the best model for use in evaluation of pharmacological and toxicological profiles. Use of an optimized diet, restricted in terms of caloric intakes, has been proposed for chronic toxicity and carcinogenicity studies in rodents. It is suggested that limiting caloric intakes to 50-80% of ad libitum consumption would result in lower body weights, decreased tumor incidences and prolonged survival in the controls. To evaluate the influence of diet on chronic toxicity and carcinogenicity studies in rats, two 104-week studies were conducted. These studies consisted of 280 CD Sprague-Dawley and 280 Fischer-344 rats fed ad libitum, and 140 CD Sprague-Dawley and 140 Fischer-344 rats fed a diet that was optimized by limiting caloric intakes by 15-35%. Both diets consisted of certified commercial diet in meal form. The optimized diet reduced weight gain approximately 50% after 100 weeks. Clinical chemistry and hematology parameters showed negligible effects of reduced diet, with the exception that serum triglycerides were lower in males and females in both strains at weeks 52 and 104. The ad libitum-fed animals had a higher incidence of pseudopregnancy, aggressiveness, foot sores and abscesses than the animals fed an optimized diet. These effects were more pronounced in the CD Sprague-Dawley rats than in the Fischer-344 rats. At the completion of the 104-week study, survival in the ad libitum fed CD Sprague-Dawley rats was approximately one-half that of the animals fed an optimized diet (39% versus 76%). The difference in survival between Fischer-344 rats fed ad libitum and those fed an optimized diet was less pronounced (78% versus 89%). A reduced incidence of palpable tissue masses in the ad libitum-fed CD Sprague-Dawley rats versus the animals fed an optimized diet reflected inability to detect small masses in the obese ad libitum-fed animals. In contrast, the leaner Fischer-344 ad libitum-fed animals had an increased incidence of palpable tissue masses. After 52 weeks, 40 animals from each strain and feeding regimen were killed and subjected to complete necropsy and histopathological examination; the remainder of the survivors was examined at the completion of the study (104 weeks). Use of an optimized diet substantially reduced the incidences of endocrine-mediated tumors in both rat strains and delayed the onset of leukemia in Fischer-344 rats. These results indicate the need to further investigate the relationship of increased caloric intakes and endocrine-mediated or strain specific tumors and support FDA's and others' positions that use of diet optimization in chronic toxicity and carcinogenicity rodent bioassays has the potential to remarkably improve the scientific quality and relevance of these studies. It also identified that the small increases in cost associated with diet optimization are far exceeded by the advantages of increased survival of animals, reduced intercurrent disease and rumor burdens, and increased ease of histopathological processing and evaluation.
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PMID:Effect of dietary optimization on growth, survival, tumor incidences and clinical pathology parameters in CD Sprague-Dawley and Fischer-344 rats: a 104-week study. 953 May 34

The AKR lymphoma-leukemia is a T lymphocyte neoplasm, most suitable as a model for human T cell malignancies. We have been interested in the process of tumor progression in the AKR lymphoma system. In the present study, two newly isolated variants, the TAU-42 and TAU-44, were characterized with respect to their biological behavior, by comparing them to a previously studied low-malignancy variant, the TAU-39. While the TAU-44 variant formed large s.c. local tumors, the TAU-42 variant formed only small growths or none at all. The TAU-42 lymphoma was found to have the highest malignant potential: it displayed very marked dissemination to spleen, lymph nodes, liver and lungs. The TAU-44 variant had an intermediate degree of metastatic potential but presented a predilection for spread to lymph nodes and spleen and was sometimes found to metastasize to peculiar organs, such as heart and pancreas. Cells derived from the different lymphoma variants varied in their immunophenotype: the highly malignant variant cells expressed more CD4 antigen than the low-malignancy one. The opposite was observed with regard to CD8. The variant cells also differed in their migrating capacity, the more malignant one exhibiting a higher motile activity. Studies on the tumor progression model of AKR lymphoma might contribute to the elucidation of the features determining the aggressiveness of T lymphocytic malignancies.
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PMID:Biological behavior and cell properties of new AKR lymphoma malignancy variants. 956 82

Because tumorigenesis frequently involves the dysfunction of cell cycle-related proteins, we examined the effect of mutations in CDK inhibitor p16 and its linked genomic loci p15, cl.B, and 1063.7 on the growth of primary adult T-cell leukemia (ATL) cells. Southern blot analysis of primary ATL cells showed a significantly higher incidence of p16 gene alteration in acute ATL than in chronic ATL [67.7% (23/34) vs. 26.1% (6/23), respectively; p<0.003]. Similarly, polymerase chain reaction (PCR) analysis of p16 exon 2 revealed a higher incidence of alteration in acute ATL than in chronic ATL [52.9% (18/34) vs. 26.1% (6/23), respectively; p<0.05]. PCR-single strand conformation polymorphism analysis of exons 1 and 2 of p16 showed no mutations in the patients, with normal pattern by Southern blotting or PCR analysis. Notably five of six chronic ATL patients with abnormal p16 genes progressed to acute crisis within 4 months. PCR analysis of the p16 linked loci 1063.7, p15 exon 2, and cl.B found homozygous deletion in 55.9%, 20.6%, and 2.9% of acute ATL cells and 39.1%, 13.0%, and 0% of chronic ATL cells, respectively, showing no relationship of homozygous deletion in either loci with disease subtypes. In most cases, deletions were seen in multiple genes, including p16. Acute ATL cells had a higher frequency of multigene deletions than chronic ATL cells [44.1% vs. 17.4%; p<0.05]. When leukemic cells were analyzed for interleukin 2 (IL-2) responsive growth, only p16 gene alteration was directly associated with leukemic cell growth activity. Among leukemic cells showing high IL-2 responsiveness, 73.1% (19/26) had p16 gene alteration vs. 27.8% (5/18) of leukemic cells that showed low IL-2 responsiveness (p<0.005). p16 gene alteration was found in 73.3% (14/19) of leukemic cells showing high autonomous growth rates but in only 40.0% (10/25) of those leukemic cells showing low autonomous growth (p<0.03). These results suggest the following: alteration of p16-related genomic regions in ATL is usually a wide rearrangement including the p16 gene; within this region, only p16 gene alteration is associated with disease aggressiveness; and p16 gene deletion may be a proximate event in leukemogenesis.
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PMID:Alteration of p16 (CDKN2) gene is associated with interleukin-2-induced tumor cell growth in adult T-cell leukemia. 1037 89

The expression of five cellular adhesion molecules (CAMs), CD54, CD58, CD11a, CD29 and CD49d, was studied in 113 B cell non-Hodgkin's lymphomas (NHL) and in normal B cells from 12 control lymph nodes. Rather than reporting the percentage of positive cells, which does not discriminate between NHL subtypes, we quantified the intensity of CAM expression using flow cytometry. Apart from CD49d the expression of all these CAMs was statistically different among the NHL subtypes as defined by the REAL classification. Low grade NHL-small lymphocytic, follicular and mantle cell lymphoma--which are derived from quiescent cells and show an indolent disease course, expressed low levels of CAMs. Conversely, high grade NHL-diffuse large cell lymphoma--which are derived from proliferating cells and are clinically aggressive, expressed high levels of CAMs. These results indicate that in malignant NHL B cell tumour growth and clinical aggressiveness may be related to the adhesive capacities of the tumour cells.
Leukemia 1999 Sep
PMID:Quantification of cellular adhesion molecules on malignant B cells from non-Hodgkin's lymphoma. 1048 95

Despite their common origin from the B-cell mature lymphoid system, small B-cell lymphomas/leukaemias represent in fact an heterogeneous group of diseases. Recent advances in immunohistochemistry and molecular techniques have improved our knowledge of the immune system and lymphoid neoplasms. An international consensus has been recently reached among pathologists and clinicians, that recognises clinico-pathological entities which are defined by a combination of morphological, immunophenotypical, genetic and clinical features. In each entity, a range of histological grade and clinical aggressiveness can be encountered. Recognition of these entities, combined with clinical prognostic factors has clinical implications in terms of response to treatment and prognosis. The purpose of this paper is to focus on a practical approach, either clinical or pathological, of the diagnosis of small B-cell lymphoma/leukaemia.
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PMID:Small B-cell lymphoproliferative disorders: an overview of diagnostic approach. 1086 48

Standard chemotherapy has been ineffective for improving the poor 10-year survival rate of patients with indolent lymphoma. However, a wider choice of therapeutic modalities has become recently available, including immunotherapy with monoclonal antibodies and allogeneic peripheral blood stem cell transplantation. Accordingly, a sensitive prognostic indicator is required to identify high-risk patients and to help design new therapeutic approaches for them. We previously reported that the serum nm23-H1 protein level was an independent prognostic factor for aggressive lymphoma. The present study was performed to assess the clinical implications of this protein on indolent lymphoma and whether it can be used to classify the aggressiveness of the disease in order to assist in the individualization of therapy. A total of 130 patients with indolent lymphoma were enrolled in this multicenter study. The serum nm23-H1 protein level was significantly higher in patients with indolent lymphoma than in a normal control group. In addition, indolent lymphoma patients with higher nm23-H1 levels had worse overall and progression-free survival rate than those with lower nm23-H1 levels. Therefore, nm23-H1 in serum may be useful for identifying a distinct group of patients at high risk.
Leukemia 2001 May
PMID:Serum nm23-H1 protein as a prognostic factor for indolent non-Hodgkin's lymphoma. 1136 46

To investigate the lymphomagenesis of NK/T lymphoma, we comprehensively and systematically analyzed the expression pattern of the human NK/T cell line (NK-YS) genome by cDNA expression array and tissue microarray. We detected significant changes in the gene expression of NK-YS cell line: an increase in 18 and a decrease in 20 genes compared to normal NK cells or peripheral blood mononuclear cells. Among these genes, we found a strong decrease in hematopoietic cell specific protein-tyrosine-phosphatase SH-PTP1 (SHP1) mRNA by cDNA expression array and reverse transcriptase-polymerase chain reaction. Further analysis with standard immunohistochemistry and tissue microarray, which used 207 paraffin-embedded specimens of various kinds of malignant lymphomas, showed that 100% of NK/T lymphoma specimens and more than 95% of various types of malignant lymphoma were negative for SHP1 protein expression. On the other hand, SHP1 protein was strongly expressed in the mantle zone and interfollicular zone lymphocytes in reactive lymphoid hyperplasia specimens. In addition, various kinds of hematopoietic cell lines, particularly the highly aggressive lymphoma/leukemia lines, lacked SHP1 expression in vitro, suggesting that loss of SHP1 expression may be related to not only malignant transformation, but also tumor cell aggressiveness. SHP1 expression could not be induced in either of two NK/T cell lines by phorbol ester, suggesting that genetic impairment or modification with methylation of SHP1 DNA could be one of the critical events in the pathogenesis of NK/T lymphoma. This evidence strongly suggests that loss of SHP1 gene expression plays an important role in multistep tumorigenesis, possibly as an anti-oncogene in the wide range of lymphomas/leukemias as well as NK/T lymphomas.
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PMID:Reduction of hematopoietic cell-specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias : combination analysis with cDNA expression array and tissue microarray. 1158 76

The present study examines the clinical significance of serum neuron-specific enolase (NSE) in patients with adult T cell-leukemia (ATL). Serum NSE values were measured using a radioimmunoassay in 35 patients (acute type, n = 15; lymphoma type, n = 10; chronic type, n = 10) and in 7 controls carrying T lymphotropic virus type-1 (HTLV-1). Serum NSE values >10 ng/mL were detected in 9 of 15 patients with acute type (60%), 5 of 10 with lymphoma type (50%), and in one of 10 patients with chronic type (10%) ATL, but in none of the HTLV-1 carriers. Contrary to previous findings demonstrating that 20% of patients with non-Hodgkin's lymphoma (NHL) had positive serum NSE, the frequency of a high NSE value in patients with acute and lymphoma type ATL was much higher (60% and 50%, respectively). The serum NSE value positively correlated with serum thymidine kinase activity (TK) and serum soluble interleukin-2 receptor (sIL-2R) levels (P < 0.04 and P < 0.01, respectively). Serum NSE values at the initial diagnosis were adversely related to overall survival time according to the log-rank test (P < 0.02). Pathological examinations demonstrated that both patients with anaplastic large cell lymphoma type ATL had cytoplasmic NSE and CD30 markers on cell membranes. These findings suggest that serum NSE is partially produced by ATL cells and that ATL tumor cells seem preferentially produce NSE compared with other NHL cells. Serum NSE may be a novel marker of disease aggressiveness as well as a prognostic factor for ATL.
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PMID:Clinical significance of serum neuron-specific enolase in patients with adult T-cell leukemia. 1235 4

We previously demonstrated that interleukin 2 (IL-2) autocrine/paracrine growth in adult T-cell leukaemia (ATL) cells was closely correlated with clinical aggressiveness. In the present study, we compared the significance of IL-15 and IL-2 in growth of ATL cells and clinical aggressiveness. Thirty-seven patients with ATL were examined: 19 acute and 18 chronic. Autonomous growth and IL-2- or IL-15-responsive growth activities of ATL cells were measured by [3H]-thymidine incorporation after 24 h cultures in vitro. All of the autonomous, IL-15- and IL-2-responsive growth activities of acute-type cells were higher than those of chronic type (P = 0.04, P = 0.03 and P = 0.02 respectively). IL-15- and IL-2-responsive growth activities were highly correlated (P = 0.0001, R2 = 0.837). Enzyme-linked immunosorbent assay (ELISA) showed detectable serum levels of IL-15 and IL-2 in 18 out of 19 and 14 out of 17 patients respectively. Reverse transcription polymerase chain reaction (RT-PCR) revealed IL-15 and IL-2 mRNA expression in 8 out of 11 patients' cells. Anti-IL-2 antibody partially inhibited autonomous growth of ATL cells; anti-IL-15 antibody was less effective. In situ immunochemistry detected IL-15 in cells of three patients and was consistent with the results of RT-PCR. These results suggest that ATL cells grow in an IL-15 autocrine/paracrine manner and that this growth is related to disease aggressiveness in a manner similar to IL-2.
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PMID:Autocrine and/or paracrine growth of adult T-cell leukaemia tumour cells by interleukin 15. 1240 87


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