1/6. review of mononuclear cell leukemia in F-344 rat bioassays and its significance to human cancer risk: A case study using alkyl phthalates.Elevated incidences of mononuclear cell leukemia (MNCL) have been observed in a number of chronic bioassays in the F-344 rat. As this tumor type is unique to the rat and is only common in the F-344 strain, its significance for human cancer risk is unclear. For this reason, a survey of the published literature was undertaken to assess the occurrence and etiology of MNCL in F-344 rats and to evaluate its potential significance to humans using alkyl phthalate data as an example. It was found that MNCL occurs in untreated, aged F-344 rats at a high and variable rate, it is uncommon in most other rat strains, and its background incidence has increased significantly over time. This complicates retrospective data interpretation. MNCL has not been found in other mammalian species and no histologically comparable tumor is found in humans. In general, a statistically significant increase in frequency of a common tumor in the F-344 rat is an insufficient basis for determining that a chemical presents a carcinogenic hazard to humans, particularly when that tumor is not observed in other species. As one example, the alkyl phthalates constitute one group of substances which has been associated with increased MNCL frequency in the F-344 rat after high dietary doses. In evaluating the significance of this increase in MNCL, an extensive toxicological database for phthalates indicates that toxicological effects occur only at relatively high doses, and tumor development (including MNCL) occurs only after an apparent threshold is exceeded. Phthalates are not genotoxic as a class, further supporting the hypothesis of the existence of a threshold. When these considerations are collectively evaluated, it can be concluded that a finding of increased MNCL in F-344 rats exposed for a lifetime to a nongenotoxic chemical is not toxicologically relevant to humans, even when MNCL is observed at an increased incidence that is statistically significant. Thus, the increased incidence of MNCL observed in F-344 rats exposed to some alkyl phthalates is likely a strain-specific effect of little or no relevance for humans, and characterization of these chemicals as carcinogens based on increased MNCL in F-344 rats is not scientifically supported.- - - - - - - - - - ranking = 1keywords = leukemia (Clic here for more details about this article) |
2/6. immunotherapy of hematologic malignancies and metastatic solid tumors in experimental animals and man.New approaches are needed for maximizing specific responses against tumor cells resistant to chemotherapy. While cytokine therapy may amplify natural resistance against minimal residual disease, more robust anti-leukemia reactivity can be provided by allogeneic bone marrow transplantation (BMT) in conjunction with myeloablative, hence hazardous, conditioning, at the cost of graft-versus-host disease (GVHD). documentation of the capacity of donor lymphocyte infusion (DLI) given late post BMT, when patients were off immunosuppression, in early 1987, with successful reversal of relapse and cure of patients fully resistant to maximally tolerated doses of chemoradiotherapy, with many patients alive and well >10-15 years later, indicated two important facts. First, resistant tumors are unlikely to be cured with higher doses of chemoradiotherapy that may harm the patient but not eliminate all his clonogenic tumor cells. Second, that under condition of tolerance to donor alloantigens, DLI may provide a cure to otherwise resistant patients. These observations paved the road for clinical application of non-myeloablative stem cell transplantation (NST), in the early 90s, based on a two-step procedure, first involving induction of transplantation tolerance to donor alloantigens by engraftment of donor stem cells, following safe lymphoablative rather than myeloablative conditioning. Second, use of donor lymphocytes for elimination of residual tumor or otherwise abnormal hematopoietic cells by immune-mediated graft-versus-host effects inducible by mobilized blood stem cell allografts containing larger inocula of donor T cells, or supported by post-grafting DLI when patients were off immunosuppressive modalities.- - - - - - - - - - ranking = 0.2keywords = leukemia (Clic here for more details about this article) |
3/6. Inflammatory fibrous histiocytoma: case report.This report concerns a patient with inflammatory fibrous histiocytoma, who in contrast to previous reported cases, has had a long survival (20 years), without evidence of recurrent disease following treatment. An interesting but nonreproducible study was the development of leukemia in 2 of 3 Swiss strain mice following the intraperitoneal injection of a saline extract of the patient's tumor.- - - - - - - - - - ranking = 0.2keywords = leukemia (Clic here for more details about this article) |
4/6. Identification of molecular variants of p210bcr-abl in chronic myelogenous leukemia.The aberrant abl protein product of a chronic myelogenous leukemia (CML) blast crisis cell line (K562) and of five philadelphia chromosome-positive CML patients in blast crisis were analyzed by an immune complex kinase assay using two antipeptide sera generated against the hydrophilic domain of v-abl and a region within the third exon of the breakpoint cluster region (bcr) respectively. Both the anti-abl and anti-bcr sera detected a 210 kd band in extracts derived from k562 cells and from two CML patients with myeloid blast crisis. p210 was detected by the anti-abl but not the anti-bcr sera in three CML patients with myeloid (one patient) and lymphoid (two patients) blast crisis, indicating the absence of bcr exon 3 in this protein. Southern blot analysis on dna derived from one of the patients in the latter group was consistent with the break on chromosome 22 occurring 5' to bcr exon 3. Our observations demonstrate that the Philadelphia translocation results in the generation of a chimeric bcr-abl protein with at least two molecular variants, both of which are enzymatically active as protein kinases.- - - - - - - - - - ranking = 1.1777013351406keywords = leukemia, bcr-abl, myelogenous, myelogenous leukemia (Clic here for more details about this article) |
5/6. T-cell leukemia with thymic involution.The prognosis of acute lymphoblastic leukemia is affected adversely by T-cell markers on the malignant lymphoblasts. Direct involvement of the thymus has been assumed because of frequent mediastinal enlargement in these patients and the important role of the thymus in certain mouse leukemias. We report here an adult with T-cell leukemia and mediastinal enlargement who had physiologic involution of the thymus. The possible role of diphenylhydantoin in the pathogenesis of this disease is reviewed. The possible usefulness of Nu/Nu mouse xenografting for the study of this lethal disorder is discussed.- - - - - - - - - - ranking = 1.4keywords = leukemia (Clic here for more details about this article) |
6/6. Parosteal lymphoblastic lymphoma. A human counterpart of Abelson virus-induced lymphosarcoma of mice.A 16-year-old girl with an unusual presentation of lymphoblastic lymphoma is described. The tumor originated as a paraspinal mass accompanied by lytic bone lesions in the pelvic bones. Neither an anterior mediastinal mass nor lymphadenopathy were noted. This pattern of disease is strikingly reminiscent of lymphomas induced in mice by the Abelson leukemia virus. This patient's lymphoma cells, unlike the usual lymphoblastic lymphoma cells, did not bear classical T-lymphocyte surface markers. A permanent cell line was derived from her tumor. Sparse amounts of cytoplasmic mu-immunoglobulin heavy chains were present in most of these cells, suggesting that the tumor originated in pre-b-lymphocytes. The phenotype of the cultured tumor cells is similar to Abelson virus-transformed murine bone marrow cells. Tumor cells of this phenotype may originate in the bone marrow and spread subsequently in and around the involved bones. This pattern of disease is distinctly different from that of T-cell lymphoblastic lymphoma, which typically presents in the mediastinum and cervical lymph nodes, and involves the bone marrow only as a late manifestation of advanced disease.- - - - - - - - - - ranking = 0.2keywords = leukemia (Clic here for more details about this article) |