Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 2 and its receptor have emerged as a central control system in the regulation of the immune response and the proliferation of T cells, B cells, and macrophage. IL-2 receptor expression is strongly associated with several forms of human lymphoproliferative disease including adult T-cell leukemia-lymphoma, hairy cell leukemia, Hodgkin's disease, and peripheral T-cell lymphoma in which it may play a pathogenetic role. IL-2 receptor expression may also play a role in some B-cell non-Hodgkin's lymphomas and histiocytic proliferations. Recent discoveries in immunology and advances in biotechnology have opened therapeutic possibilities for IL-2 including the use of anti-Tac monoclonal antibodies and immunoconjugates for the therapy of Tac-positive lymphoproliferative disease, the use of anti-Tac monoclonal antibodies as novel immunosuppressants, and the use of genetically engineered recombinant IL-2 and activated autologous lymphocytes in the adoptive immunotherapy of cancer. Therapeutic and diagnostic applications of IL-2 continue to be defined.
 ...
PMID:Interleukin receptors in lymphoid lesions. Relevance to diagnosis, biology, and therapy. 267 80

Hairy cell leukemia (HCL) has been shown to be extraordinarily sensitive to treatment with alpha-interferon (IFN). In order to define clinically effective IFN doses associated with minimal toxicity, the therapeutic efficacy and side effects of recombinant IFN-alpha-2C treatment of HCL were compared for two different dose regimens: 18 patients (group A) received conventional doses of recombinant IFN-alpha-2C (2 x 10(6)U/m2) for a median time of 35 weeks (range 26-52 weeks), and 21 patients (group B) received optimum biological response-modifying doses of IFN-alpha-2C (0.2-0.6 x 10(6)U/m2) for a median time of 31 weeks (range 12-52 weeks). Interferon was administered daily subcutaneously for 3 months and then every second or third day. Induction of neopterin excretion was chosen as the marker for definition of biological response. The smallest IFN dose causing maximum in vivo induction of biosynthesis of the GTP-degradation product neopterin was deemed "biologically optimal." Both dose regimens were effective, but the low-dose regimen was almost free of toxicity. Thus, in HCL patients alpha-IFN related toxicity can be separated from its antineoplastic activity. Low doses of alpha-IFN should be considered for treatment of HCL patients who develop toxic side effects and for primary treatment of HCL patients with severe cytopenia.
Leukemia 1989 Jun
PMID:Comparison of clinical efficacy and toxicity of conventional and optimum biological response modifying doses of interferon alpha-2C in the treatment of hairy cell leukemia: a retrospective analysis of 39 patients. 272 61

Hairy cells are classified as B cell tumors at a preplasma cell stage of differentiation and are believed to represent cells undergoing a switch process. These cells are stimulated in vitro to DNA synthesis and multiplication in the presence of the lymphokine LMW-BCGF. We have tested the level of expression on these cells of the newly described B8.7 activation marker which has been reported to be associated with the capacity of various B cells to respond to LMW-BCGF. The presence of this marker has been readily detected on the hairy cells of 10 of the 12 patients tested in this study; interestingly, for one of the negative cases, the tumor cells were unable to proliferate in response to LMW-BCGF. As on normal B cells, a marked inhibition of the LMW-BCGF dependent response could be achieved in the presence of a monoclonal anti-B8.7 antibody, sustaining the proposal that the B8.7 molecule is involved in the signaling pathway of this growth factor. IFN-alpha is highly efficient in the therapy of hairy cell leukemia (HCL), and we confirm in the present study that IFN-alpha also inhibits the LMW-BCGF dependent proliferation of hairy cells in vitro. In addition, we show that this inhibition is independent of a significant modulation of the B8.7 antigen, a molecule putatively associated with the LMW-BCGF receptor.
Leukemia 1989 May
PMID:Expression of the B8.7 antigen on hairy cells and relation with the LMW-BCGF response. 278 22

The serum of children with untreated hemophagocytic syndromes contains elevated levels (23,600 to 75,200 U/mL) of soluble interleukin-2 receptor (SIL2R) that returns toward normal with clinical improvement. These levels are in excess of levels previously reported for benign conditions. They are as high as levels reported for HTLV-1-associated adult T-cell leukemia (HATL) and hairy cell leukemia (HCL) in adults and some children with poor-prognosis non-T, non-B, acute lymphoblastic leukemia (ALL). Serum SIL-2R is a marker of disease activity that has the potential to identify infants at risk for the inherited form of the disease before the disease is clinically expressed.
 ...
PMID:Elevated soluble interleukin-2 receptor in childhood hemophagocytic histiocytic syndromes. 278 34

It is not clear whether cells from various chronic B cell leukemias including B-chronic lymphocytic leukemia (CLL), CLL in prolymphocytoid transformation (CLL-PLT), B-prolymphocytic leukemia (PLL), and hairy cell leukemia (HCL) simply represent different stages of a single B cell differentiation pathway. Furthermore, it is not known whether cells from any given B cell leukemia are characterized by the same population during the differentiation process. Differentiation of various B cell leukemic cells was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and the resulting changes in their morphology, cytoplasmic immunoglobulin (clg), and cytochemistry were evaluated. With respect to peculiar morphological change, i.e. extending long thin processes (spreading) and the appearance of clg, each sample showed different responses. According to these two indices samples were classified into three groups; spread+ clg- samples (one case of CLL-PLT, all HCL), spread+ clg+ samples (one of CLL, one of CLL-PLT), and spread- clg+ samples (a majority of CLL, one of CLL-PLT, and all PLL). Unexpectedly, both CLL and CLL-PLT consisted of heterogenous populations as to the reactivity to TPA. In the process of TPA-induced differentiation in CLL cells, features similar to those of HCL cells were not found. Since three different TPA-induced response patterns were observed in each chronic B cell leukemia type, it was not possible to sequentially assign each of these leukemias along a single B cell differentiation pathway. In order to explain this result, we introduced the hypothesis that these groups might be divided into different lineages in B cell differentiation. Since TPA-induced spreading cells were present in the B cell fraction of normal peripheral blood mononuclear cells, this morphological change should not be associated with malignant transformation.
Leukemia 1989 Jul
PMID:The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on leukemic cells from chronic B cell leukemia. 278 98

Malignant B cells, derived from hairy cell leukemia (HCL), non-Hodgkin's lymphoma (NHL) or prolymphocytic leukemia were stimulated with mitogens and interleukin 2 after careful depletion of contaminating T cells resulting in final residual percentages of less than 0.1. No proliferation was found as measured by 3H-thymidine incorporation. Subsequently, to the non-T B cell cultures very small amounts of autologous or allogeneic T cells were added, ending up in final concentrations of 0.1, 0.5, 1, or 2% T cells. It appeared that a marked proliferation occurred which had in various coculture combinations to be ascribed to the T cells alone. Moreover, most HCL and other B cell NHL additionally stimulated the T cells, resulting in a further increase in proliferation. We conclude that 3H-thymidine incorporation by malignant B cells such as HCL and B-NHL stimulated with mitogens and IL-2 will in most cases wrongly be attributed to proliferation by the B cells themselves, and instead has to be ascribed to contaminating T cells.
Leukemia 1989 Oct
PMID:Residual T lymphocytes, and not malignant B cells, proliferate upon mitogenic stimulation. 278 26

Hairy cell leukemia is a preplasmacytic B cell leukemia which is not EBV associated, although elevated titers of Epstein-Barr virus (EBV) antibodies have been seen in this leukemia and chronic lymphocytic leukemia. Hairy cells are not readily susceptible to EBV infection in vitro, even though they are EBV receptor-positive B cells. We have observed a 59-year-old patient who after 9 years of hairy cell leukemia developed a well-differentiated IgG-kappa monoclonal B cell lymphoma without further evidence of hairy cell leukemia. Pathologically, the lymphoma showed plasmacytic differentiation, and in the patient's serum, a 2 g/dl monoclonal IgG-kappa component was present. DNA extracted from the lymphomatous lymph node hybridized with DNA fragments of a reiterated sequence of EBV, IR1. The transformation, with no chemotherapy involved, from a preplasmacytic leukemia into a lymphoplasmacytic lymphoma with monoclonal gammopathy may be related to the entry of EBV into these cells. Studies at the molecular level may help understand mechanisms of malignant transformation or interconversion in lymphoproliferative disorders of the B cell type.
Leukemia 1987 Apr
PMID:Transformation of hairy cell leukemia to EBV genome-containing aggressive B cell lymphoma. 282 16

Human T cell leukemia virus (HTLV-II) is an infrequently encountered human T cell leukemia virus first isolated from a patient with atypical hairy cell leukemia. Recently, we identified a second patient infected with HTLV-II who had a similar clinical syndrome of atypical hairy cell leukemia associated with peripheral T cell lymphocytosis. HTLV-II was detected by molecular hybridization studies, and more recently, by electron microscopy, in cell lines derived from the patient. Both patients came from the Los Angeles area and had spent several years in Alaska. As opposed to our two patients, 21 patients with more typical cases of hairy cell leukemia were seronegative for HTLV-II. Two additional cases of unusual T cell malignancy linked to HTLV-II have been described by other investigators and bear limited similarity to our index cases. Further studies are necessary to define the spectrum of malignancies linked to HTLV-II and to identify infected individuals for prospective study.
Leukemia 1987 Apr
PMID:Relationship between human T cell leukemia virus-II and atypical hairy cell leukemia: a serologic study of hairy cell leukemia patients. 282 18

Sera from 11 Japanese patients with hairy cell leukemia and 4B122, an anti-hairy cell serum produced by the authors, were surveyed by Western blot analyses for cross-reacting antibodies to human T cell leukemia virus (HTLV)-I and -II virions released, respectively, from Lma-66 and Mo-T cell lines. Sera from the majority of the patients showed positive reactions with p15, p19, and/or p24 of HTLV-I and with p21 and/or p22 or HTLV-II. 4B122 was weakly cross-reactive with HTLV-II but not with HTLV-I. These results militate against the involvement of HTLV-I or -II but may implicate a role by a cross-reacting, previously unrecognized retrovirus in the pathogenesis of hairy cell leukemia in Japanese patients.
Leukemia 1987 Apr
PMID:Cross-reacting antibodies to human T cell leukemia virus-I and -II in Japanese patients with hairy cell leukemia. 282 19

We previously reported isolation of human T-cell leukemia virus II (HTLV-II) from a second patient (N.R.A.) with atypical hairy cell leukemia. Follow-up analysis of the characteristics of the patient's HTLV-II infection over a 2-year period has revealed that the patient had two coexistant lymphoproliferative disorders. Oligoclonally integrated HTLV-II was detected in DNA extracted from the patient's peripheral blood mononuclear cells on separate occasions greater than 1 year apart, similar to integration of HTLV-I seen in adult T cell leukemia/lymphoma. Although integrated provirus was readily detected, no HTLV-II viral RNA expression was seen in fresh peripheral blood lymphoid cells. Although the patient's peripheral blood consistently contained a majority of atypical lymphoid cells with a T cell antigenic phenotype, he ultimately developed extensive pleural, hepatic and soft tissue infiltration with malignant Tac+, tartrate-resistant, acid phosphatase-positive (TRAP+) B cells of clonal origin. To further characterize the role of HTLV-II, the patient's peripheral blood mononuclear cells were fractionated into four enriched subpopulations at autopsy. Oligoclonally integrated HTLV-II was detected in DNA from a T cell-enriched fraction and a CD8+ T cell-enriched fraction, but not in a CD4+ T cell-enriched fraction, a non-T cell fraction, or in B cells obtained from the malignant pleural effusion. We conclude that the patient harbored two distinct lymphoproliferative disorders, a TRAP+, Tac+ B cell malignancy consistent with hairy cell leukemia that did not contain HTLV-II and a Tac-, CD8+ lymphoproliferative syndrome with oligoclonally integrated HTLV-II.
 ...
PMID:Integrated human T-cell leukemia virus II genome in CD8 + T cells from a patient with "atypical" hairy cell leukemia: evidence for distinct T and B cell lymphoproliferative disorders. 282 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>