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)

A number of mitogens was used in 21 chronic B-lymphocytic leukaemia patients. Thymidine uptake assays were performed to evaluate cell stimulation. Phytohemagglutinin and phorbol-myristate 13 acetate were found to be the most efficient on cell proliferation. Abnormal clones were found 7 times with PMA, 4 times with PHA, twice with pokeweed, but in no case with lipopolysaccharide or proteine-A. The efficiency of PHA as a B-cell activator is likely to be due to T cell mediation.
...
PMID:Use of various mitogens and cell stimulation index in 21 patients with chronic lymphocytic leukaemia. 281 75

Inosine monophosphate dehydrogenase (IMPD) is an important enzyme in de-novo purine synthesis. The level of IMPD activity has been suggested to determine whether acute leukaemia cells proliferate (if the activity is high) or differentiate (if IMPD activity is low). IMPD activity measured by the conversion of inosine monophosphate to xanthine monophosphate ranged from 12.5 to 87.0 (mean 49.4) pmol/h/10(6) cells in normal bone marrow. The levels were significantly raised in AML (range 14-374, mean 184 pmol/h/10(6) cells) and ALL (range 65-228, mean 172 pmol/h/10(6) cells). Normal tonsillar (B) lymphocytes showed higher levels (range 78-159, mean 110 pmol/h/10(6) cells) than resting peripheral blood T lymphocytes (range 8.8-51.2, mean 28.1 pmol/h/10(6) cells). In CLL, the results (range 19-173, mean 64.3 pmol/h/10(6) cells) were comparable to those of normal tonsillar B lymphocytes. IMPD levels could be related to cell cycle in PHA-stimulated lymphocytes, since IMPD activity increased in parallel with increase in DNA synthesis measured by labelled thymidine incorporation. On the other hand, IMPD activity did not correlate with the proportion of proliferating cells measured on a FACS sorter in either AML or ALL or in normal tonsillar B cells. We conclude that IMPD levels are higher in B than T lymphocytes and in acute leukaemia blasts compared to more differentiated mixed bone marrow cells. The results do not suggest, however, that IMPD assay will be of value in differentiation of the various subtypes of acute leukaemia or of malignant haemopoietic cells from the equivalent normal cell at the same level of differentiation.
...
PMID:Inosine monophosphate dehydrogenase activity in acute leukaemia. 288 46

beta-Hexosaminidase (EC 3.2.1.20; Hex) activity and isoenzyme characteristics were analyzed in human normal and leukemic leukocytes. Unseparated CLL and CML cells had a specific activity that was lower, whereas ALL and AML blasts had a higher specific activity than normal lymphocytes and granulocytes. CLL B-cells had a lower specific activity compared with that in normal non-T-lymphocytes; CLL T-cells and normal T-cells had similar activity. Isoenzyme separation was performed by chromatofocusing on PBE-94 coupled with an automated enzyme assay. When using a single linear pH elution gradient, normal leukocytes and all leukemia cells contained two forms of isoenzyme (B and A). When a double pH elution gradient was performed, an extra distinct form of Hex (I) was recorded. Hex I was present in small amounts in normal granulocytes and PHA-stimulated normal lymphocytes; isoenzyme I was found in high amounts in all leukemias tested. The activity ratios I/B and I/A, as well as the I isoenzyme profile, may facilitate differentiation between normal and leukemic cells and between lymphoblastic and myeloblastic leukemias.
...
PMID:Alteration of beta-hexosaminidase activity and isoenzymes in human leukemic cells. 294 28

Human T-cell leukemia virus (HTLV)-infected cell lines derived from adult T-cell leukemia (ATL) express constitutively the receptor for Interleukin-2 (IL-2-R) and the associated antigen (Tac antigen). In contrast, the same antigen is transiently expressed by normal T-cells only after immune stimulation. Recently, it was reported that the constitutively expressed Tac antigen on ATL cells and cell lines was not down-regulated or modulated by anti-Tac antibody. Since the antigen was modulated on normal mitogen- or alloantigen-stimulated T-cells, we postulated that the regulation of IL-2-R may be abnormal on ATL cells; the synthesis of IL-2-R is continuously stimulated in these cells. A unique HTLV/ATLV(-) cell line (YT) derived from a child with acute lymphoblastic leukemia was found to express low levels of Tac antigen that could be enhanced by various stimuli, including conditioned medium (CM) derived from normal lymphocytes, but not by lectins (PHA, Con A). Of particular interest, the exposure of YT cells to CM from ATL cell lines with helper phenotype revealed the presence of factor(s) (ATL-derived factor, ADF) that augmented the synthesis and expression of IL-2-R/Tac antigen on YT cells and promoted YT cell growth. CM from HTLV(-) leukemia cell lines lacked both IL-2-R augmenting activity and a growth promoting activity. Immunoaffinity-purified IL-2 and recombinant gamma interferon also lacked IL-2-R augmenting activity. Moreover, the physicochemical analysis with Fast protein liquid chromatography (FPLC) revealed that ADF was quite different in pI point from the IL-2-R augmenting activity in CM from normal lymphocytes. These results suggested that ADF is a unique product of HTLV(+) cells. The possible relationship between ADF production, HTLV infection, and the abnormal expression of IL-2-R is suggested, and these abnormalities may be advantageous for the leukemogenesis and abnormal growth of ATL.
...
PMID:Adult T leukemia cells produce a lymphokine that augments interleukin 2 receptor expression. 297 23

We investigated the growth and differentiation of leukaemia B cells from patients with B-cell chronic lymphocytic leukaemia (CLL) in response to proliferation and differentiation factors present in conditioned medium and to anti-immunoglobulin antibodies. Highly purified E-rosette negative (E-) B cells from 5 out of 15 patients with CLL exhibited moderate proliferative responses to 10 or 50 micrograms/ml of F(ab)'2 fragments of rabbit anti-human mu-chain specific antibody. Conditioned medium (CM), derived by stimulating human peripheral blood mononuclear leucocytes with PHA, induced significant proliferative responses of purified E- cells in 13 out of 14 patients examined. The extent of these proliferative responses varied substantially, and was in the range of 2.6- to 91-fold. Stimulation of purified E- cells from patients with CLL with both anti-mu and CM resulted in significant proliferation in all 15 patients examined. These responses were significantly higher than those induced by CM alone (P less than 0.02). Synergism between CM and anti-mu in inducing proliferative responses was observed in 11 out of 15 patients. Largely leukaemic B cell populations expressing on the cell surface more than one immunoglobulin heavy-chain isotype, exhibited significantly higher (P less than 0.009) proliferative response to CM and anti-mu than those expressing IgM only. Highly purified E-peripheral blood or tonsil lymphocytes from all normal donors examined responded by proliferation to anti-mu alone or to CM alone. Synergism in inducing proliferative responses was also observed when the cells were stimulated with both CM and anti-mu. In addition to inducing proliferative responses, culture with CM of purified E-rosette negative, largely leukaemic, B cells from patients with CLL for 6 days at 37 degrees C resulted in differentiation into immunoglobulin synthesizing and secreting cells. Synthesis and secretion of IgM were observed in 7 out of 10 patients examined. A switch to IgG production was observed in three patients. Morphological examination of E- cells from patients with CLL after treatment with CM demonstrated that these cells were differentiated into plasma-like cells. These results suggest that leukaemic B cells from patients with CLL can be induced to proliferate and differentiate in response to growth and differentiation factors derived by mononuclear leucocytes, in a manner similar to that of normal B cells.
...
PMID:Induction of proliferation and differentiation of leukaemic B cells from patients with chronic lymphocytic leukaemia by anti-mu and conditioned medium. 311 Sep 41

The morphology, immunophenotype, cytoenzymatic and functional activities of T lymphocytes from 4 patients with chronic lymphoproliferative disease of T-cell origin were studied. Clonal proliferation was demonstrated by distinctive chromosomal abnormalities involving chromosomes 2 and 14. Patients 1 and 2 were classifiable as OKT4+ T-cell chronic lymphocytic leukaemia (T-CLL) and patient 3 as OKT4+/OKT8+ T-CLL, with helper function in vitro only in patient 1. Patient 4 has low-grade lymphocytosis with benign clinical course, with cells showing morphology of large granular lymphocytes (LGL), and immunophenotype HNK-1+, ER+, Fc gamma receptor+, OKT3+, OKT11+ and OKT8+, as well as natural killer activity, radiosensitive suppressor activity on Ig secretion and responsiveness to PHA; this case was interpreted as LGL leukaemia. This study indicates that a large proportion of cases of true T-CLL may belong to the OKT4 subset, and that extensive investigations should be made of the lymphocytic OKT8+/T gamma forms to characterize them precisely.
...
PMID:Functional and multimarker analysis of T-cell chronic lymphocytic leukaemia. 315 72

After culture with 20-30% autologous or allogeneic T cells and PHA, at least a proportion of the pathological cells from a variety of B-cell proliferations (common acute lymphoblastic leukaemia, prolymphocytic leukaemia, non-Hodgkin's lymphoma with blood involvement by mature lymphoid (cleaved and non-cleaved) cells) expressed true endogenous sheep erythrocyte (E) receptors. In contrast, plasma cells and a variety of myeloid cells failed to express E receptors after similar in vitro stimulation. These data, taken in conjunction with previous findings with B cells from normals and patients with hairy-cell and chronic lymphocytic leukaemia, suggest that B cells earlier than plasma cells can express E receptors after appropriate stimulation. The findings provide an in vitro counterpart of the leukaemic proliferations expressing both E receptor and surface immunoglobulin described from various laboratories, and further question the lineage specificity of the E receptor.
...
PMID:Stimulated lymphoid cells of B lineage, but not plasma or myeloid cells, can express E receptor. 315 85

The effect of large granular lymphocyte leukemia on F344 rat lymphocytes was studied by analyzing the blastogenic responses of normal spleen cells exposed to serum from leukemic rats. Sera from both transplanted as well as spontaneous cases of LGL leukemia markedly depressed the response to ConA and PHA. The suppressive activity was heat-stable at 56 degrees C, non-dialyzable and was effective even when added to lymphocytes only during the last 24 hrs of culture. A similar depression of blastogenesis was caused by sera from nonleukemic fasted rats. Depletion of lipoproteins from sera partially relieved the suppression. Leukemic and fasted rats had nearly identical serum lipoprotein electrophoretic profiles, indicating that abnormal lipoprotein metabolism may result from the severe anorexia which characterizes the terminal stages of the disease and may cause immunosuppression. Residual suppressive activity was also found in lipoprotein depleted sera. Supernatant fluids from spleen cell cultures of some leukemic rats also depressed lymphocyte blastogenic responses when compared to supernatants from normal spleen cultures.
...
PMID:Inhibition of in vitro mitogen-induced lymphoproliferative responses by sera from F344 rats with large granular lymphocyte leukemia. 325 32

In this paper we describe a gene that lies 85 kb 5' of the constant region of the human alpha chain and some 30-50 kb 3' of the alpha chain V region (H. Griesser, unpublished observation). This gene undergoes somatic recombination and is transcribed in thymocytes, PHA-stimulated peripheral blood T cells, and some T cell leukemic cell lines. Sequence analysis revealed that the gene has a structure similar to that of immunoglobulin and other T cell antigen receptor genes. Comparison of the sequence to a mouse gene found in a similar location revealed 80% homology at the protein level. Recently, M. Davis and A. Weiss (personal communication) have demonstrated that the protein product of the mouse gene is the delta chain gene. Thus, the gene described in this paper represents the human homolog of the delta chain gene of the T cell antigen receptor.
Leukemia 1988 Nov
PMID:The isolation of the human delta chain gene and its expression in normal T cells and T cell leukemias. 326 56

In the PHA-leukocyte feeder colony assay--a fluid assay on top of an agar underlayer--colonies might not be the product of clonogenic cells but rather from aggregates, as was already shown for hairy cell leukemia (Leukemia Res. 11, 911 (1987)). To study the role of aggregation in this colony assay in other B-cell malignancies, we irradiated cells from B-chronic lymphocytic leukemia, B-non-Hodgkin's lymphoma and multiple myeloma. In nearly all cases, viable "colonies" were seen after irradiation, albeit in lower numbers. These data indicate that in the PHA-leukocyte feeder colony assay, a considerable percentage of colonies from a large variety of B-cell malignancies originate from aggregating rather than from proliferating cells.
...
PMID:Radioresistant pseudo-colony formation in the PHA-leukocyte feeder colony assay. 326 67


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