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)

The normal counterparts of the B cells found in hairy cell leukemia (HCL) are not known. We report here a detailed morphological, cytochemical, immunological and molecular analysis of a patient with B-cell chronic lymphocytic leukemia (B-CLL) who later in the course of his disease developed hairy cell leukemia. We speculate that hairy cell transformation of B-CLL might be related to an in vivo protein kinase C mediated cellular activation of B-CLL cells.
Leukemia 1991 Feb
PMID:Hairy cell transformation of a B-cell chronic lymphocytic leukemia: a morphological, cytochemical, phenotypic and molecular study. 167 87

Human T-cell leukemia/lymphoma virus type I (HTLV-I) was discovered in 1980, and it subsequently was found to be the cause of adult T-cell leukemia/lymphoma. A progressive neurologic disease known as tropical spastic paraparesis, or HTLV-I-associated myelopathy, has also been linked to infection with HTLV-I. A related virus, HTLV type II (HTLV-II), has been isolated from patients with hairy-cell leukemia, but it has not been proved to be the cause of any disease. In late 1988, US blood banks began screening all blood donations for antibodies to HTLV-I/II. This program has resulted in the identification of many unexpectedly seropositive blood donors and provided much information about the prevalence of HTLV-I/II in the United States. In this article, I review the replication of these agents, as well as their pathogenesis, diagnosis, and mechanisms of spread.
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PMID:Human T-cell leukemia/lymphoma viruses. Life cycle, pathogenicity, epidemiology, and diagnosis. 167 95

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 first high performance liquid chromatographic method for determination of the plasma concentration of 2-chloro-2'-deoxyadenosine (CdA) in patients, which is significantly more sensitive than the previously used RIA method, is presented. CdA is a purine analogue with useful clinical activity against lymphoproliferative disorders and it has recently been found to be the single most active agent in the treatment of hairy cell leukaemia. Guaneran (6-nitroimidazol-6-thioguanine) was added to 1 mL plasma as the internal standard and CdA was extracted using ethyl acetate. A Perkin-Elmer C18, 3 mu, 8 cm column was used for the separation of CdA and the internal standard from endogenous compounds in the sample with a mixture of sodium phosphate buffer 10 mM, methanol and acetonitrile (85:10:5, pH = 3.0) as the mobile phase. The sensitivity of the method (1 nM) allows the determination of CdA in plasma 24 h after the administration of 0.14 mg/kg as a 2 h infusion.
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PMID:Determination of 2-chloro-2'-deoxyadenosine in human plasma. 168 27

Anti-SSEA-1 which binds to glycoconjugates with a Gal beta 1-4(fuc alpha 1-3)GlcNAc epitope and VIM-2 which binds to gangliosides with a NeuAc alpha 2-3GlcNAc beta-4(FUC alpha 1-3) GlcNAc beta 1-3Gal-epitope were used to determine the expression of their corresponding carbohydrate antigens in human leukocytes and leukemia cells. Expression of these antigens was evaluated by immunohistochemical staining of plastic embedded sections of bone marrow or isolated cells, and by immunostaining of isolated glycosphingolipids separated by thin layer chromatography. The expression of both antigens was restricted to normal and leukemic myeloid cells. A range of positive immunohistochemical staining was found among normal marrow myeloid precursors, with myeloblasts giving weaker staining than more mature cells (promyelocytes, myelocytes, metamyelocytes). A similar trend was observed with leukemia cell lines, in that the myeloblastic cell line KG1 was weakly stained compared to the partially differentiated cell line HL-60. Immunohistochemical staining of marrows from acute leukemia patients showed that the VIM-2 antigen is more strongly expressed than the SSEA-1 antigen. Interestingly, both antibodies stained AMMoL cells more intensely than AML cells. Granulocytes from marrows of chronic myelogenous leukemia (CML) patients were intensely stained by both antibodies, whereas lymphocytic leukemias (acute lymphocytic, chronic lymphocytic and hairy cell marrows) were negative. Thus, although both antigens are restricted to myeloid cells there are differences in the level of expression depending on the level of cell maturity. Immunostaining of glycosphingolipids isolated from myeloid cells demonstrated that the SSEA-1 epitope is carried by several neutral glycosphingolipids and that the VIM-2 epitope is carried by three or more gangliosides. Major SSEA-1 glycosphingolipids, with seven to more than ten monosaccharides, are expressed by all myeloid cells regardless of the level of maturity, although quantitative differences are apparent in different patient samples. Two strongly immunoreactive VIM-2 gangliosides with ten and twelve monosaccharides, respectively were found in myeloid cells. The ratio of these two gangliosides varied dramatically, with greater amounts of the more complex ganglioside being present in most cell samples. Normal neutrophils and CML cells had much greater quantities of the VIM-2 gangliosides than acute leukemia cells. This observation correlates with our earlier findings that: (1) acute leukemia cells have less total ganglioside than granulocytes and (2) acute leukemia cells have a predominance of short chain gangliosides (i.e. less than five monosaccharide units). Finally, both CML cells and normal neutrophils express a shorter chain VIM-2 ganglioside, which was not detected in acute myelogenous leukemia cells.
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PMID:Distribution of VIM-2 and SSEA-1 glycoconjugate epitopes among human leukocytes and leukemia cells. 169 Mar 17

Progress in genetics now enables the synthesis of molecules acting on the regulation of the immune system which are called cytokines. Currently there are several cytokines, Interferon (IFN), Interleukin 2 (IL2), tumour necrosis factor (TNF) as well as haematopoietic growth factors and these are the object of study in clinical trials. Interferon has already been used in the therapy of hairy cell leukaemia, Kaposi sarcoma associated with AIDS(SIDA) and metastasis of malignant melanoma. Interleukin 2 allows for an increase in the cytotoxic activity of NK cells in producing LAK cells, the lymphocyte infiltrating the tumour (TIL). Therapeutic combinations combining IL2 associated with LAK or of TIL have been evaluated in some private studies. These treatments have shown some interesting response levels on those tumours which are usually resistant, such as malignant melanoma or carcinoma of the kidney. TNF is active in vitro on human tumours; its potential toxicity is important; it is the object of a phase 1 clinical trial. Haematopoietic growth factors, G-CSF and GM-CSF, stimulate the production of leucocytes which will be valuable to correct toxic affects on the marrow during chemotherapy. This will enable chemotherapy to be given at a high dose.
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PMID:[Immunotherapy of cancer using cytokinins. Use and perspectives in lung oncology]. 169 91

Interferons are proteins with antiviral, antiproliferative, and immune-regulating activity. They are classified as alfa, beta, or gamma on the basis of antigenicity and biologic properties. Alfa interferons as single-agent therapy produce clinical improvement in approximately 90 percent of patients with hairy-cell leukemia, and up to 70 percent of patients with chronic myelogenous leukemia (CML) in early-stage disease. Prolonged suppression or elimination of the leukemic cell clone by interferon may ultimately increase survival of patients with CML. Interferon is not effective single-agent therapy for multiple myeloma, but improves response rate when combined with conventional agents. AIDS-associated Kaposi's sarcoma demonstrates a 40 percent objective response rate to interferon, with less risk of immune system suppression than conventional cytotoxics. Other applications of alfa interferon include malignant melanoma and renal cell carcinoma. Beta interferon is similar to the alfa subtype and may have utility in treatment of brain tumors. Gamma interferon is an important immune regulator with qualitative and quantitative differences in its efficacy and toxicity when compared with alfa interferon.
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PMID:Clinical use of biologic response modifiers in cancer treatment: an overview. Part I. The interferons. 169 95

Immunoprecipitation of radioiodinated hairy cell leukaemia (HCL) cell lysates with monoclonal antibody (MoAb) HML-1, originally reported to recognize intraepithelial T cells, and with MoAb B-ly7, originally reported to react with HCL, led to identical biochemical characteristics. In SDS-PAGE under reducing conditions, a major band of 143 kDa, a broad band ranging from 112 to 122 kDa, and two additional faint bands of 175 and 100 kDa could be determined. Deglycosylation of N-linked sugar moieties by treatment of immunoprecipitates with endoglycosidases indicated that the two main protein cores of the antigen are predominantly if not exclusively glycosylated by complex and hybrid types of oligosaccharide chains. Competitive binding inhibition demonstrated that both MoAb are directed against different epitopes. Immunohistochemically, the staining patterns obtained with both MoAb in normal tissues, in T- and B-cell lymphomas, and in HCL were identical except for a single case of HCL which was HML-1-/B-ly-7+. We conclude that MoAb HML-1 and B-ly7 recognize the same antigen.
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PMID:Identity of HML-1 antigen on intestinal intraepithelial T cells and of B-ly7 antigen on hairy cell leukaemia. 169

The promising results obtained with Fludara I.V. (fludarabine phosphate) treatment in the common indolent B-cell neoplasms have led to their further evaluation in other unusual B-cell malignancies, in Hodgkin's disease, and in T-cell diseases. A significant response rate has been found among patients with macroglobulinemic lymphoma, those with prolymphocytic leukemia or prolymphocytoid variant of chronic lymphocytic leukemia, and those with mycosis fungoides. The limited therapeutic data in hairy-cell leukemia and in Hodgkin's disease are also interesting.
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PMID:Fludarabine phosphate therapy in other lymphoid malignancies. 169 85

Fludara I.V. (fludarabine phosphate) is a purine analogue with a high level of activity in a variety of indolent lymphoproliferative malignancies, including chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin's lymphomas (NHL), cutaneous T-cell lymphoma, macroglobulinemia, and hairy-cell leukemia. The high response rate in relapsed and refractory patients with CLL suggests that Fludara I.V. is the most active single agent for this condition. Nevertheless, a number of issues for the future development of Fludara I.V. must be considered: the optimal dose, schedule, and route of administration (intravenous v oral) remain to be determined. To improve on single-agent results, combinations of Fludara I.V. with other agents are under development for patients with CLL and NHL. Phase III clinical trials will be performed to compare Fludara I.V. with standard therapy versus the combination regimen in previously untreated patients with CLL. A similar study is under consideration for low-grade NHL. Companion immunologic and biologic studies will be an integral component of these trials to provide a more rational approach to staging and treatment, and to increase our knowledge of the biology of these disorders.
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PMID:Issues for the future development of fludarabine phosphate. 169 86


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