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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess potential differences in genetic predisposition to myeloid neoplasia, we evaluated the karyotypes and reviewed results of cytogenetic studies on bone marrow specimens from six patients with myelodysplastic syndrome, or acute myeloid leukemia, and a history of solid tumor managed solely by surgical resection. Structural or numerical deletions of chromosome 5 were identified in each of four patients with abnormal marrow karyotypes. Constitutional karyotypes were normal in two patients studied with clonal marrow chromosome abnormalities. Review of previously reported cases of myeloid neoplasia following resection of solid tumors disclosed a preponderance of chromosome 5 deletions. Predisposition to specific chromosome loss may influence genetic expression of disease in solid tumor patients developing hematologic malignancy.
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PMID:Predominance of chromosome 5 deletions in myeloid neoplasia associated with solid tumors managed by surgical excision. 155 Oct 74

Leukemic intracranial space occupying lesions are rare. A 69 year old man with acute myelogenous leukemia was found to have an intracranial leukemic mass at the time of his remission period. Computed tomography and magnetic resonance imaging study demonstrated a large irregular mass in the right temporal lobe. After total removal of the tumor, the patient was treated with whole brain irradiation and intrathecal chemotherapy. After surviving for 7 months, the patient expired of hematologic relapse.
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PMID:Intracerebral leukemic mass in acute myelogenous leukemia. 156 Feb 56

The p53 gene is currently considered to function as a tumor-suppressor gene in various human malignancies. In hematologic malignancies, alterations in the p53 gene have been shown in some human leukemias and lymphomas. Although mutations in the p53 gene are infrequent in acute myelogenous leukemia (AML) patients, we show in this report that alterations in the p53 gene are frequent in myeloid leukemia cell lines. We studied alterations of the p53 gene in nine human myeloid leukemia cell lines by reverse transcriptase-polymerase chain reaction (RT-PCR), single-strand conformation polymorphism (SSCP) analysis, and direct sequencing. Expression of the p53 gene was not detected at all by RT-PCR in two of the nine cell lines. In these two cell lines, Southern blot analysis showed gross rearrangements and deletions in both of the p53 alleles. Six of the nine cell lines were found to express only mutant p53 mRNA by RT-PCR/SSCP analysis and direct sequencing, and wild-type p53 mRNA was not detected. Two of the mutant p53 mRNAs were shown to be products of abnormal splicing events induced by intronic point mutations. Taken together, eight of nine human myeloid leukemia cell lines expressed no or an undetectable amount of wild-type p53 mRNA. Three of the eight cell lines were growth factor-dependent. Our results suggest that inactivation of the p53 gene may be a common feature in myeloid leukemia cell lines and may play an important role in the establishment of these cell lines.
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PMID:Frequent mutations in the p53 gene in human myeloid leukemia cell lines. 157 49

Interleukin-6 (IL-6) has been shown to inhibit growth and induce differentiation of several myeloid leukemia cell lines. In this work, two in vivo models of acute myeloid leukemia (AML) in mice have been used to test the therapeutic potential of recombinant human IL-6. In mice inoculated by a transplantable AML tumor, IL-6 injections inhibited the development of leukemia and increased survival. The effect was related to dose and length of treatment. In a model of radiation-induced leukemogenesis in SJL/J mice, administration of low-dose IL-6 for 10 days, 4 months after irradiation, reduced the incidence of leukemia observed during 1 year, whereas granulocyte-macrophage colony-stimulating factor (GM-CSF) increased the incidence of leukemia. In vitro liquid cultures of leukemic blood cells obtained from AML patients showed that IL-6 slowed growth and decreased the proportion of blasts with an increase in more mature myeloid elements in 72% of M1, M2, M4 AML cases. In contrast, GM-CSF less often produced differentiation but stimulated leukemic cell growth in liquid cultures, without synergism by IL-6.
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PMID:Antitumor effects of human recombinant interleukin-6 on acute myeloid leukemia in mice and in cell cultures. 157 51

Beta-2-microglobulin (B2m) was measured in the cerebrospinal fluid (CSF) and serum from 18 adults with acute lymphoblastic leukemia, acute myeloblastic leukemia or lymphoma in order to detect early central nervous system (CNS) involvement or relapse. Six had CNS-involvement documented by neurologic symptoms and tumor cells in the CSF. Their CSF-B2m-concentrations were significantly higher before intrathecal chemotherapy than in those without this complication (P less than 0.01). During therapy CSF-B2m levels fell rapidly to normal values on repeated measurements. The study demonstrates that serial determination of CSF-B2m alone may be a useful and sensitive marker of CNS-dissemination in acute leukemia and malignant lymphoma. Using the criteria of CSF-B2m greater than 160 nmol/l as a positive diagnostic test the sensitivity of the test was 100%, the specificity was 76%. The same values for the CSF/serum-ratio greater than 1 were 75% and 64%, respectively.
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PMID:Cerebrospinal fluid beta-2-microglobulin in adult patients with acute leukemia or lymphoma: a useful marker in early diagnosis and monitoring of CNS-involvement. 157 9

The purpose of this study is to describe the incidence and survival of childhood cancer in the West Midlands for the period 1980-1984. Proportional breakdown by Asian subgroup is also considered. A total of 587 patients were registered, 49 of them of Asian origin. Breakdown to Asian versus non-Asian subgroups by diagnosis revealed comparatively high rates for Hodgkin's disease, retinoblastoma and neuroblastoma in the Asian patients. However, a deficit of cases was seen for CNS tumours. Comparison of overall age-standardized rates (ASR) for all cancers revealed a substantially lower value compared to that reported for the USA white population but a similar value to the USA black and UK white populations. Diagnostic breakdown revealed that the major difference between the West Midlands Regional Children's Tumour Research Group (WMRCTRG) and the USA white ASR was in the leukaemia and lymphoma group. Overall survival for the series was 56% at 5 years. The poorest prognosis was found in acute myeloid leukaemia, with only 23% of patients surviving at 5 years, against 62% in acute lymphoblastic leukaemia. CNS tumours also had a poor outcome, with an overall survival rate of 47%, although certain individual diagnoses were more favourable. We observed a 100% survival rate in Hodgkin's disease up to 5 years from diagnosis, and both Wilms' tumour and retinoblastoma had 90% survival rates.
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PMID:Childhood cancer in the West Midlands: incidence and survival, 1980-1984, in a multi-ethnic population. 158 36

Three patients with T-cell lymphoblastic lymphoma and peripheral blood eosinophilia are reported. At the time of diagnosis, all patients had lymphadenopathy, and one had a mediastinal mass. Lymph node biopsies revealed lymphoblastic lymphoma admixed with a variable number of mature eosinophils. Immunophenotypic studies demonstrated that each lymphoma had an immature T-cell immunophenotype. Bone marrow biopsies were hypercellular with myeloid hyperplasia and eosinophilia but were negative for lymphoma. All patients received multiagent chemotherapy; one patient achieved a complete remission, and two patients had partial remissions. All patients subsequently developed a myeloid malignancy. Two died of acute myeloid leukemia within 18 months of the diagnosis of lymphoblastic lymphoma. The third patient relapsed with a lymphoma that had histologic and immunophenotypic features of both T-cell lymphoblastic lymphoma and granulocytic sarcoma and also developed a poorly defined myeloproliferative disorder. These findings suggest that T-cell lymphoblastic lymphoma associated with eosinophilia may represent a distinct clinico-pathologic entity with a high risk of subsequent myeloid neoplasia.
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PMID:T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. 844 14

Interleukin-2 (IL-2) therapy generates killer cells with major histocompatibility complex (MHC)-unrestricted cytotoxicity against most tumors but not normal tissues. Cyclosporine A (CsA) has been reported to break tolerance to self and to induce killer cells with specificity against class II MHC (Ia) antigens both on the host and the tumor cells, resulting in a mild graft-versus-host disease (GVHD) in an autologous bone marrow transplantation (BMT) setting in the rat. We used these two agents in a syngeneic BMT model in a strain of mice that does not develop GVHD with CsA. Therapy with either agent alone was ineffective, whereas a combination of CsA plus IL-2 after BMT induced a potent graft-versus-tumor (GVT) effect against a melanoma and an acute myeloid leukemia. The antitumor effect could be adoptively transferred by infusing spleen cells harvested from mice treated with CsA plus IL-2 into secondary recipients that received chemoradiotherapy. The cytotoxicity of these cells was not influenced by treatment of tumor cells with gamma-interferon or Ia antibody. The cytotoxic effect was mediated by Thy 1+ and asialo GM 1+ cells. There was no GVHD either in the primary recipients of CsA and IL-2 or in those receiving the adoptively transferred spleen cells. Our findings show that combination therapy with CsA and IL-2 after syngeneic BMT induces a potent GVT effect in a non-MHC-restricted manner, and point to the existence of differences between the mechanisms of GVT and GVHD.
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PMID:Synergism of interleukin-2 and cyclosporine A in induction of a graft-versus-tumor effect without graft-versus-host disease after syngeneic bone marrow transplantation. 161 Oct 84

Myelodysplastic syndromes originate from a pluripotent stem cell. This view, previously suggested by G-6-PD and cytogenetic investigations, has been established unequivocally by X-chromosome inactivation analysis based on DNA polymorphisms and by studies of mutated oncogenes. Two genomic alterations associated with MDS have been analyzed in more detail. Activation of the RAS oncogenes, preferentially N-RAS, is demonstrated in approximately 35% of MDS patients. Mutations in the FMS gene, encoding the CSF-1 receptor, are found in 16% of cases. Interestingly, RAS and FMS mutations are predominantly observed in disorders of myelomonoctic differentiation, i.e., the CMML subtype in MDS and the AML FAB type M4. Moreover, homozygous deletion of the FMS gene may be an important event in the genesis of the MDS variant 5q- syndrome. Preliminary data indicate that defects in tumor-suppressor genes, namely p53, may also contribute to the development of MDS. Different lines of evidence suggest that clinical preleukemia is preceded by a phase in which genetic alterations accumulate without any hematologic change. Cases in point are the detection of RAS and FMS mutations in healthy individuals who had been treated in the past with cytotoxic therapy for lymphoma, the frequent observation of clonal remission in AML patients, or the identification of oncogene mutations in healthy individuals without even a history of malignancy or chemotherapy. Possibly, either germline mutations of oncogenes or tumor-suppressor genes and the process of genomic imprinting may constitute additional factors that predispose hematopoietic stem cells to malignant transformation. Limited as they are, the currently available data suggest that accumulation of genomic lesions, rather than their precise order of development with respect to one another, characterize the multistep process of leukemogenesis in which MDS already represent more advanced stages. The prognostic significance of oncogene mutations in MDS patients is controversially discussed. This issue awaits prospective analyses taking into account the influence of treatment modalities. However, the clinical relevance of molecularly defined parameters has already been established for their use as clonal markers in determining the mode of action and efficiency of different therapeutic approaches.
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PMID:Molecular genetic aspects of myelodysplastic syndromes. 161 6

Expression of the normal p53 gene promotes cell differentiation, maturation and apoptosis. The mutant p53 gene, which does not function normally, is frequently expressed at elevated levels in tumor cells [for review see Lane, D.P. & Benchimol, S. (1990). Genes Dev., 4, 1-8]. We have analysed the expression of and mutational change in the p53 gene in the peripheral blood cells of 49 primary acute myeloid leukemia (AML) patients. The p53 protein levels were elevated in 37 patients (75%) when measured by immunoprecipitation with antibodies PAb1801 and PAb421, which recognize both normal and mutant forms of the protein. The p53 protein from 32 of these 37 patients was immunoprecipitated by PAb240, which recognizes a conformation of p53 protein associated with point mutations. However, point mutations were detected by single-stranded conformation polymorphism (SSCP) assay and direct sequencing in only three patients at codons 178, 245, 273 and 290. Growth stimulation of normal lymphocytes also generated p53 which was immunoprecipitable by PAb240. Thus, alteration of p53 conformation, rather than acquisition of point mutations, could be the mechanism underlying the increased proliferation of myeloid cells in most AML patients.
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PMID:Altered conformation of the p53 protein in myeloid leukemia cells and mitogen-stimulated normal blood cells. 163 Aug 24


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