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)

We have previously shown that total T cells derived from lymph nodes (LN) involved by Hodgkin's disease (HD) secrete higher levels of colony-stimulating activity than total T cells present within benign hyperplastic (BH) LN and B-non-Hodgkin's lymphoma (B-NHL) LN, suggesting that T cells with particular properties accumulate in HD LN. To further characterize this T-cell population, we have quantified production of both granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) production in a total of 98 T-cell clones (TCC) derived from CD25+ activated T cells present in HD LN; TCC derived from CD25+ T cells obtained from B-NHL LN(101 TCC), BH LN(95 TCC), and peripheral blood (PBL; 38 TCC) of healthy donors were used as controls. HD LN were characterized by the presence of an elevated number (44%) of TCC producing particularly high titers of both GM-CSF and M-CSF, whereas only a minority of such TCC was found in control groups (10% in B-NHL, 16% in BH, 8% in PBL). These observations support the hypothesis of a selection of T-cell families with particular properties occurring in contact with Reed-Sternberg (RS) cells. According to the biological properties of GM-CSF and M-CSF, it seems reasonable to suggest the involvement of this particular subset of T cells in the granulomatous process, the peripheral blood polynucleosis, and in the paracrine growth of RS cells.
Leukemia 1992 Aug
PMID:Accumulation of T-cell clones producing high levels of both granulocyte-macrophage and macrophage colony-stimulating factors (CSF-1) in lymph nodes involved by Hodgkin's disease. 164 Jul 35

Chemotherapy cures a minority of adult tumours (e.g. Hodgkin's and non-Hodgkin's lymphoma, acute leukaemia, teratoma) and the majority of childhood tumours. Prolongation of survival by chemotherapy has been shown for small cell lung cancer, ovarian cancer and breast carcinoma (when used as an adjuvant). However, in the majority of solid tumours there is a less than 20% response to chemotherapy and even curable tumours may relapse and become resistant. Resistance may be de novo, acquired as a stable change within the cell, or be rapidly inducible within the cell after drug administration. Several mechanisms have been described including multidrug resistance, glutathione transferases and DNA repair. Understanding these mechanisms may help to improve the therapeutic ratio and develop new approaches.
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PMID:Drug resistance. 165 Jun 21

The authors retrospectively reviewed the clinicopathologic and immunologic features of 65 consecutive cases of childhood lymphoma reported between 1980 and 1989. Southern blot hybridization was also performed in 23 cases to study their association with Epstein-Barr virus (EBV) and human T-cell leukemia virus type 1 (HTLV-1). The 65 cases included 56 non-Hodgkin's lymphoma (NHL) (86%) and 9 Hodgkin's disease (HD) (14%). The NHL could be classified into the following groups: Group I, small noncleaved cell lymphoma (20 cases); Group II, lymphoblastic lymphoma (17 cases); Group III, large cell lymphoma (17 cases); and miscellaneous (2 cases). There was no follicular lymphoma case. Immunohistochemical study on paraffin sections and/or frozen specimens in 47 cases of NHL showed that all the Group I cases belonged to B-cell neoplasm (17 of 17 cases); most of the Group II cases belonged to T-cell neoplasm (9 of 14 cases); and most of the Group III cases were peripheral T-cell lymphoma (PTL) (8 of 16 cases), including 2 cases of Ki-1 lymphoma. The majority of childhood NHL belonged to high-grade malignancy with an aggressive clinical course (median survival time, 8 months). The EBV DNA could be detected from the tumor tissues in 4 of 6 PTL, but in none of the remaining 19 cases of NHL including 6 Burkitt's type lymphomas. HTLV-1 proviral genome was not detected in all specimens examined. The authors concluded that the distribution pattern and clinicopathologic feature of childhood lymphoma in Taiwan are comparable to that in Japan and western countries. The frequent association of EBV with aggressive PTL was unique and deserves additional investigation.
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PMID:A pathologic study of childhood lymphoma in Taiwan with special reference to peripheral T-cell lymphoma and the association with Epstein-Barr viral infection. 165 30

This review first considered some general problems in establishing causal links between a virus and a human cancer and offered some guidelines in the pursuit of this objective. Second, it reviewed the current causal associations for several candidate oncogenic viruses in relation to the tumors with which they are associated. These include Epstein-Barr virus in relation to Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, and non-Hodgkin's lymphoma; hepatitis B and C viruses in relation to hepatocellular carcinoma; human T-cell leukemia/lymphoma virus type 1 and atypical leukemia/lymphoma; and human papilloma viruses in relation to cervical carcinoma. For some, the causal relationship is strong: hepatitis B virus with hepatocellular carcinoma, and human T-cell leukemia/lymphoma virus with adult T-cell leukemia/lymphoma. For one, the causal relationship is moderate: Epstein-Barr virus with African Burkitt's lymphoma. For others it is incomplete or inconclusive: Epstein-Barr virus with Hodgkin's disease and non-Hodgkin's lymphoma, and hepatitis C virus with hepatocellular carcinoma. Current techniques do not permit an answer for some: human papilloma virus with cervical carcinoma.
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PMID:Viruses and cancer. Causal associations. 166 91

Multidrug resistance describes an experimental observation which appears to explain cross-resistance to certain structurally unrelated cytotoxic agents, including anthracyclines, vinca alkaloids and podophyllotoxins. It is now clear that a major factor responsible for its development is increased expression of a membrane glycoprotein--P-glycoprotein, which functions as an energy-dependent efflux pump. Recent data, particularly in haematological malignancies such as acute non-lymphocytic leukaemia, myeloma and non-Hodgkin's lymphoma, indicate that P-glycoprotein may be involved in the development of clinical drug resistance. The potential therefore exists for new therapeutic studies aimed at circumventing resistance which develops through this mechanism, by using modulators, such as verapamil, quinidine and several others, which prevent cellular drug efflux by competitive binding to P-glycoprotein.
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PMID:Multidrug resistance: clinical relevance in haematological malignancies. 167 35

Most of the circulating lymphocytes from three asymptomatic adults (one male, two female, age range 61-67 years) with isolated persistent lymphocytosis of between 7.1 and 10 x 10(9)/l possessed characteristic villous projections of the cell membrane. Morphological, histochemical, ultrastructural, immunological, and genotypic studies confirmed a clonal proliferation of tartrate-resistant acid phosphatase (TRAP)-negative CD5-CD10-CD25- and CD11c+ B-cells. In addition to CD11c, these cells expressed other adhesion receptors (LFA-1/CD11a, VLA-4/CD29/49d, ICAM-1/CD54, and LAM-1) and produced detectable amounts of interleukin-1 beta, interleukin-6, and in one case tumour necrosis factor-alpha mRNA. This monoclonal villous lymphocytosis (MVL) could be differentiated from B-cell chronic lymphocytic, prolymphocytic, and hairy cell leukaemias, and from previously recognized CD11c+ chronic B-cell leukaemia. A rare splenomegalic non-Hodgkin's lymphoma variant with circulating villous B-lymphocytes (SLVL), usually CD10+ and sometimes CD11c- and TRAP+, appears to be a closely related disorder. In all three patients the lymphocyte count increased very slowly, at a rate less than 5 x 10(9)/l per year, over 3-7.5 years of follow up, and a moderate splenomegaly eventually developed in one of the patients. Chemotherapy was never required. MVL may be a relatively benign clinical entity akin to SLVL within the group of CD11c+ B-cell lymphoproliferative disorders.
Leukemia 1991 Sep
PMID:Monoclonal lymphocytosis with villous lymphocytes: a chronic lymphoproliferative disease of CD11c+ B-cells. 168 36

The leucocyte adhesion molecule LFA-1 (CD11a/CD18) and its counter structure ICAM-1 (CD54) play a pivotal role in cell-cell interactions in the immune system and hence their expression on malignant cells might play an important role in determining the biological behavior of lymphoid malignancies. This study examined the LFA-1 (CD11a/CD18) and ICAM-1 (CD54) expression profiles of a large series of non-Hodgkin's lymphomas (NHL, n = 220) and lymphoid leukemias (LL, n = 48), which, by their differentiation-antigen phenotype represented essentially all stages of lymphoid development from stem cell to mature activated T- and B-lymphocyte. It was found that NHL and LL differentially express LFA-1 and ICAM-1 molecules according to their lineage derivation, stage of differentiation, and growth pattern. Specifically: (a) T-cell neoplasms nearly always express LFA-1 whereas B-cell tumors are often LFA-1 low/negative; (b) ICAM-1 expression is largely confined to tumors with a mature or activated T- or B-cell phenotype; (c) neoplasms with a leukemic dissemination pattern are either ICAM-1 low or negative. Importantly, neither LFA-1 nor ICAM-1 expression was related to tumor grade.
Leukemia 1991 Oct
PMID:Expression of the leucocyte integrin LFA-1 (CD11a/CD18) and its ligand ICAM-1 (CD54) in lymphoid malignancies is related to lineage derivation and stage of differentiation but not to tumor grade. 168 77

This article presents data from the phase I and II clinical investigations of Fludara I.V. (fludarabine phosphate) (NSC 312887), which is the 5'-phosphorylated derivative of the novel antimetabolite, 9-beta-D-arabinofuranosyl-2-fluoroadenine. The comprehensive phase I evaluation of this new antitumor agent was conducted in 51 patients with advanced malignancy and 15 additional patients with aggressive forms of leukemia. Three separate phase I schedules of drug administration were examined. Myelosuppression was the dose-limiting toxicity on each schedule administered to patients with solid tumors. The drug was also examined at higher doses in patients with leukemia, and the dose-limiting toxicity on the high-dose protocol was unacceptable: serious neurologic toxicity. The observation of antitumor responses in patients with advanced non-Hodgkin's lymphoma prompted additional phase II investigation in patients with lymphoproliferative malignancy. The encouraging phase II data demonstrate that Fludara I.V. has promise for patients with low-grade histologic subtypes of non-Hodgkin's lymphoma and chronic lymphocytic leukemia. While interesting additional basic and clinical research projects regarding Fludara I.V. remain, it is important to expeditiously pursue approval for this drug. Adequate data exists to demonstrate that the low-dose administration of Fludara I.V. is both safe and effective. While the development of this drug has stimulated renewed interest in the clinical investigation of the chronic lymphoproliferative malignancies, the time for making it readily available to these patients has arrived.
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PMID:A comprehensive phase I and II clinical investigation of fludarabine phosphate. 169 82

In 1978, Cancer and Leukemia Group B initiated a randomized study to determine the usefulness of the addition of bleomycin and/or high-dose methotrexate to standard therapy for the treatment of certain adult non-Hodgkin's lymphomas. Between 1978 and 1985, 177 patients with diffuse large cell lymphoma (DLCL) and 97 patients with other intermediate-grade non-Hodgkin's lymphoma were randomized to receive therapy with three courses of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) every 3 weeks with or without low-dose bleomycin by continuous IV infusion. Responders after three courses were further randomized to 3 weeks of therapy with either high-dose methotrexate (3 gm/m2/week intravenously with leucovorin rescue) or standard-dose methotrexate (30 mg/m2/week orally without rescue). Therapy was concluded with three additional courses of CHOP. Neither the addition of low-dose infusion bleomycin nor the use of high-dose rather than low-dose methotrexate had significant effects on response for patients with DLCL; complete response rates for the four treatment programs ranged from 47% to 51%. Median failure-free survival (FFS) for the entire group of DLCL patients was 12 months; 5-year FFS was 27%. There was no significant effect on FFS from the addition of either low-dose bleomycin to CHOP (5-year FFS: CHOP, 28%; CHOP-B, 26%, P = 0.81), or from the use of different doses of methotrexate (5-year FFS: high-dose, 34%; standard-dose, 33%, P = 0.51). Patients with follicular large cell lymphoma, with or without diffuse areas, had a better FFS (5-year FFS, 47%) than patients with DLCL (5-year FFS, 27%), while the patients with the other histopathologic subtypes of diffuse lymphomas had the poorest FFS (5-year FFS, 16%).
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PMID:A randomized comparison of methotrexate dose and the addition of bleomycin to CHOP therapy for diffuse large cell lymphoma and other non-Hodgkin's lymphomas. Cancer and Leukemia Group B study 7851. 169 53

Detailed immunophenotypic analyses of immunologically classified leukemias and lymphomas showed that CD40 displays an exquisite B-lineage specificity within the human lymphopoietic system. Notably, 82% of B-lineage chronic lymphocytic leukemias (CLLs), 82% of B-lineage hairy cell leukemias (HCLs), 86% of B-lineage non-Hodgkin's lymphomas (NHLs), and 29% of B-lineage acute lymphoblastic leukemias (ALLs) were CD40+. Quantitative analyses of the correlated expression of CD40 and other B-lineage differentiation antigens on fetal lymphoid precursor cells by multiparameter two-color/three-color flow cytometry, combined with analyses of sequential antigen expression on fluorescence-activated cell fluorescence activated cell sorter (FACS) isolated immunologically distinct fetal B-cell precursor subpopulations during in vitro proliferation and differentiation, provided evidence that the acquisition of CD40 antigen in human B-cell ontogeny occurs subsequent to the expression of CD10 and CD19 antigens but before the surface expression of CD20, CD21, CD22, CD24, and surface immunoglobulin M (sIgM). Some leukemic pro-B cells from ALL patients as well as normal pro-B cell clones from fetal livers displaying germline Ig heavy chain genes were CD40+, indicating that the acquisition of CD40 antigen likely precedes the rearrangement of Ig heavy chain genes. CD40+ FACS-sorted malignant cells from B-lineage ALL as well as B-lineage NHL patients were capable of in vitro clonogenic growth, indicating the CD40 antigen is expressed on clonogenic leukemia and lymphoma cells. This hypothesis was confirmed by the ability of an anti-CD40 immunotoxin that we used as an antigen-specific cytotoxic probe to effectively kill clonogenic B-lineage ALL and NHL cells.
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PMID:Temporal association of CD40 antigen expression with discrete stages of human B-cell ontogeny and the efficacy of anti-CD40 immunotoxins against clonogenic B-lineage acute lymphoblastic leukemia as well as B-lineage non-Hodgkin's lymphoma cells. 170 26


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