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)

Four patients with chronic lymphatic leukaemia, M. Hodgkin and metastatic breast carcinoma developed particularly severe generalised herpes zoster, with complications of herpes zoster pneumonia, signs of encephalitis and phrenic nerve paresis. Virus specific complement-fixing antibodies increased regularly or delayed, without strict correlation to the clinical course. However, in all these cases there was a relative or absolute deficiency of T-lymphocytes in the peripheral blood, as a result of the underlying illness and of treatment with cytostatic agents. Because of the vital role of cell-mediated immunity in the control of the varicella-zoster virus (VZV), the observed T-cell deficiency seems to be an important pre-condition for the development of severe generalised herpes zoster.
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PMID:[Severe generalized courses of zoster due to cellular immunologic defects. Importance of an absolute or relative T-cell deficiency]. 30 13

Natural resistance in vivo was studied by injecting non-immunized mice with leukaemia cells prelabelled with the thymidine analogue 131I-iododeoxyuridine. There was a decrease in the survival of the leukaemia cell inoculum as determined by whole-body gamma counting, and a failure of the leukaemia cells to survive in the spleens of mice which were not H-2 identical with the transplant. H-2-associated resistance could be measured within 24 h of leukemia inoculation and was strongest in the spleen and absent from the liver. Although all strains of mice tested were able to resist H-2 non-identical cells, resistance in irradiated (800--900 R) mice was restricted to certain strains and their F1 hybrids, notably those of the C57BL family. Resistance in both non-irradiated and irradiated mice was not due to classical immunological rejection. Mice with either genetic or induced T-cell deficiency showed full resistance, and circulating preformed antibody could not account for the rejection observed. Treatment with silica or with 89Sr abrogated natural resistance in non-irradiated as well as irradiated animals; these treatments had previously been shown to abolish both bone-marrow graft rejection in irradiated mice and in vitro natural killing. Resistance against leukaemia transplantation in irradiated C57BL mice appeared to depend on Hh-1 (H-2D) incompatibility between the host and the graft, again suggesting that bone-marrow graft rejection, and perhaps natural killer activity, is a subset of a more general paraimmune or non-adaptive rejection mechanism.
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PMID:H-2 associated resistance to leukaemia transplantation: natural killing in vivo. 624 61

Purine nucleoside phosphorylase (PNP) was recognized more than 30 years ago as a potential target for the treatment of patients with T-cell malignancies when an inherited deficiency of PNP was reported to be associated with a profound T-cell lymphopenia. The biochemical basis for this T-cell deficiency was subsequently shown to be related to the accumulation of plasma 2'-deoxyguanosine (dGuo) and intracellular dGuo triphosphate (dGTP). These observations have led to a search for PNP inhibitors that would be useful clinically in the management of T cell-derived malignancies. The most potent inhibitor of PNP described to date is forodesine, a rationally designed, transition-state analogue inhibitor. The preclinical and clinical pharmacology of forodesine showed its effectiveness in inhibiting PNP and augmenting dGuo levels in plasma. Increased dGTP concentrations in leukemia cells of different lineages provides strong support for the potential use of this agent in the treatment of patients with hematologic malignancies of both T- and B-cell origin.
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PMID:Pharmacology and mechanism of action of forodesine, a T-cell targeted agent. 1808 47

Stem cells are central to the development and maintenance of many tissues. This is due to their capacity for extensive proliferation and differentiation into effector cells. More recently it has been shown that the proliferative and differentiative ability of stem cells decreases with age, suggesting that this may play a role in tissue aging. Down syndrome (DS), is associated with many of the signs of premature tissue aging including T-cell deficiency, increased incidence of early Alzheimer-type, Myelodysplastic-type disease and leukaemia. Previously we have shown that both hematopoietic (HSC) and neural stem cells (NSC) in patients affected by DS showed signs of accelerated aging. In this study we tested the hypothesis that changes in gene expression in HSC and NSC of patients affected by DS reflect changes occurring in stem cells with age. The profiles of genes expressed in HSC and NSC from DS patients highlight pathways associated with cellular aging including a downregulation of DNA repair genes and increases in proapoptotic genes, s-phase cell cycle genes, inflammation and angiogenesis genes. Interestingly, Notch signaling was identified as a potential hub, which when deregulated may drive stem cell aging. These data suggests that DS is a valuable model to study early events in stem cell aging.
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PMID:A systems biology approach to Down syndrome: identification of Notch/Wnt dysregulation in a model of stem cells aging. 1941 98

Analysis of cancer risk in primary immune deficiency (PID) offers insight into the relationship between immune function and cancer. Data on Australian patients (n = 1132) notified voluntarily to the Australasian Society of Clinical Immunology and Allergy PID Registry (1990-2008) were linked with national death and cancer registries. Person-years of follow-up commenced from up to 15 years before registration on the PID Registry or January 1982, the inception of national cancer registration. Site-specific, 5-year age-, sex-, calendar year-, and state-standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs) were calculated for all cancers except nonmelanocytic skin cancer. During an average of 16 person-years follow-up, a 1.6-fold excess relative risk of cancer was observed (n = 58; SIR 1.60, 95% CI 1.22-2.07) for all PID combined. Relative risk was increased for non-Hodgkin lymphoma (n = 16; SIR 8.82, 95% CI 5.04-14.30), leukemia (n = 4; SIR 5.36, 95% CI 1.46-13.73), and stomach cancer (n = 3; SIR 6.10, 95% CI 1.26-17.84). Excess cancer risk was observed for predominantly antibody deficiencies and other well-defined immunodeficiency syndromes. Results suggest that predominantly antibody deficiencies may be associated with a narrower range of solid cancers than immunodeficiency characterized by predominantly T-cell deficiency, such as iatrogenic and HIV-related immunodeficiency, although this requires confirmation in larger cohorts.
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PMID:Are antibody deficiency disorders associated with a narrower range of cancers than other forms of immunodeficiency? 2079 38