Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The phospholipid composition and cholesterol content of lymphocytes from bovine blood, lymph, lymph-nodes and spleen were studied. The cholesterol/phospholipid molar ratio in the normal lymphocytes of blood and spleen was found to be about two times higher than that in the normal lymphocytes from lymph and lymph-nodes. On lymphocytic leukemia the cholesterol/phospholipid molar ratio of the blood lymphocytes decreased sharply, whereas that in lymph and lymph-nodes lymphocytes was unaffected.
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PMID:[Phospholipid composition of lymphocytes from normal and leukemic blood, lymph, lymph nodes and spleen of cattle]. 73 17

An inherited deficiency of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) produces selective lymphopenia and immunodeficiency disease in humans. Previous experiments have suggested that lymphospecific toxicity in this condition might result from the selective accumulation of toxic deoxyadenosine nucleotides by lymphocytes with high deoxycytidine kinase, levels and low deoxynucleotide dephosphorylating activity. The present experiments were designed to determine if deoxyadenosine analogs which are not substrates for adenosine deaminase might similarly be toxic toward lymphocytes and lymphoid tumors. Two such compounds, 2-chlorodeoxyadenosine and 2-fluorodeoxyadenosine, at concentrations of 3 nM and 0.15 microM, respectively, inhibited by 50% the growth of human CCRF-CEM malignant lymphoblasts in vitro. Each was phosphorylated in intact cells by deoxycytidine kinase accumulated as the nucleoside triphosphate, and inhibited DNA synthesis more than RNA synthesis. Both deoxynucleosides had significant chemotherapeutic activity against lymphoid leukemia L1210 in mice.
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PMID:Deoxycytidine kinase-mediated toxicity of deoxyadenosine analogs toward malignant human lymphoblasts in vitro and toward murine L1210 leukemia in vivo. 625 65

Purine nucleoside phosphorylase deficiency leads to a dGTP-mediated T-lymphopenia, suggesting that an analogue of deoxyguanosine would be selectively effective in T-cell disease. 9-beta-D-Arabinofuranosylguanine (ara-G) is relatively resistant to hydrolysis by purine nucleoside phosphorylase and selectively toxic to T cells, but its low solubility has prevented its use in the clinic. 2-Amino-6-methoxy-arabinofuranosylpurine (GW506U) serves as the water-soluble prodrug for ara-G. A Phase I trial in patients with refractory hematological malignancies demonstrated that the clinical responses to this agent were directly related to the peak levels of ara-G 5'-triphosphate (ara-GTP) in target cells. The aim of the present study was to develop and test strategies to increase intracellular accumulation of ara-GTP in primary human leukemia cells of myeloid and B-lymphoid origin. Three strategies were tested. First, incubations with 100 microM ara-G for 4 h produced a linear median accumulation rate of 19 microM/h (range, 2-45 microM/h; n = 15) in lymphoid leukemia cells and 16 microM/h (range, 0.5-41 microM/h; n = 11) in myeloid leukemia cells. Saturation of ara-GTP accumulation was achieved only after 6-8 h exposure in both lymphoid and myeloid leukemia cells, suggesting a rationale for prolonged infusion. Second, a dose-dependent increase in ara-GTP accumulation was observed with incubations of 10-300 microM ara-G for 3 h. Hence, dosing regimens that achieve high plasma levels of ara-G during therapy may increase cellular levels of ara-GTP. Finally, a biochemical modulation approach using in vitro incubation of leukemia cells with 10 microM 9-beta-D-arabinofuranosyl-2-fluoroadenine for 3 h, followed by either 50 or 100 microM ara-G for 4 h, resulted in a statistically significant median 1.3-fold (range, 1.1-9.0-fold; P = 0.034) and 1. 8-fold (range, 0.9-10.6 fold; P = 0.018) increase in ara-GTP compared to cells incubated with ara-G alone. Extension of these studies to ex vivo incubations confirmed our in vitro findings. These strategies will be used in the design of clinical protocols to increase ara-GTP accumulation in leukemia cells during therapy.
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PMID:Pharmacological and biochemical strategies to increase the accumulation of arabinofuranosylguanine triphosphatein primary human leukemia cells. 981 3

IL-7 is produced by stromal cells and is the major lympho- and thymopoietic cytokine. IL-7 induces proliferation and differentiation of immature thymocytes, and protects thymocytes from apoptosis by induction of bcl-2 expression. The regulation of IL-7 production is poorly characterized, although down-regulation by transforming growth factor-beta (TGF-beta) has been described. We measured the serum levels of IL-7 before and after bone marrow transplant (BMT) in 32 children undergoing BMT for genetic diseases (severe combined immune deficiency (SCID) and thalassemia), aplastic anemia, and acute lymphoblastic and non-lymphoblastic leukemia (ALL and ANLL). Prior to BMT, the highest IL-7 levels were observed in patients with SCID and ALL, i.e. those patients with genetic or acquired lymphopenia. Patients with thalassemia and ANLL had normal levels of IL-7. Over the 8 weeks following BMT, the IL-7 levels of patients with SCID and ALL fell as the absolute lymphocyte count (ALC) increased. No detectable change in IL-7 levels was observed in the patients with thalassemia and ANLL. Levels of IL-7 were highest in the young infants with SCID compared to the age-matched controls. Together, the data demonstrate that serum levels of IL-7 in lymphopenic patients are inversely related to patient age and the absolute lymphocyte count (ALC). The inverse relationship to ALC suggests that there is either direct regulation of stromal production or more likely, binding of secreted IL-7 to lymphocytes expressing IL-7 receptors.
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PMID:Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count. 1023 Nov 40

Alemtuzumab is a humanized monoclonal antibody directed against lymphocytes through the CD-52 receptor, an antigen being found on > 95% of peripheral blood lymphocytes and monocytes, and to a smaller extent on granulocytes. It is an effective immunotherapeutic agent in patients with malignancies such as non-Hodgkin lymphoma, B cell chronic lymphocytic leukemia and T cell pro- lymphocytic leukemia. Adverse side effects are increasingly recognized in patients receiving alemtuzumab, mainly including fever, rigors, nausea/vomiting, skin rash; other severe alemtuzumab-related reactions have also been described, such as lymphopenia and neutropenia leading to both opportunistic (e.g. cytomegalovirus) and non-opportunistic infections. Digestive complications have more rarely been described, i.e.: gastroenteritis and peritonitis. We recently observed a case of particular interest as the patient with T cell prolymphocytic leukaemia treated with alemtuzumab, exhibited symptomatic reactivation of CMV infection and developed subsequently typhlitis.
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PMID:Typhlitis as a complication of alemtuzumab therapy. 1756 96

Expression of a NUP98-HOXD13 (NHD13) fusion gene leads to myelodysplastic syndrome in mice. In addition to ineffective hematopoiesis, we observed that NHD13 mice were lymphopenic; the lymphopenia was due to a decrease in both T and B lymphocytes. Although the pro-B cell (B220(+)/CD43(+)) populations from the NHD13 and wild-type mice were similar, the NHD13 mice showed decreased pre-B cells (B220(+)/CD43(-)), indicating impaired differentiation at the pro-B to pre-B stage. Thymi from NHD13 mice were smaller and overexpressed Hoxa cluster genes, including Hoxa7, Hoxa9, and Hoxa10. In addition, the NHD13 thymi contained fewer thymocytes, with an increased percentage of CD4(-)/CD8(-) (double-negative (DN)) cells and a decreased percentage of CD4(+)/CD8(+) (double-positive) cells; the DN1/DN2 population was increased and the DN3/DN4 population was decreased, suggesting a partial block at the DN2 to DN3 transition. To determine clonality of the thymocytes, we used degenerate RT-PCR to identify clonal Tcrb gene rearrangements. Five of six NHD13 thymi showed an unusual Tcrb gene rearrangement pattern with common, clonal DJ rearrangements, but distinct V-D junctions, suggesting a marked clonal expansion of thymocytes that had undergone a DJ rearrangement, but not completed a VDJ rearrangement. Taken together, these findings demonstrate that expression of the NHD13 transgene inhibits lymphoid as well as myeloid and erythroid differentiation, results in overexpression of Hoxa cluster genes, and leads to a precursor T cell lymphoblastic leukemia/lymphoma.
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PMID:A NUP98-HOXD13 fusion gene impairs differentiation of B and T lymphocytes and leads to expansion of thymocytes with partial TCRB gene rearrangement. 1984 Nov 79