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)

CD7 is a single-domain Ig superfamily molecule expressed on human T and NK cells, as well as on cells in the early stages of T, B, and myeloid cell differentiation. CD7 is highly expressed on malignant immature T cells and is generally absent on malignant mature T cells, such as CD4+ Sezary leukemia and HTLV-1+ adult T-cell leukemia cells. Because of lack of identification of a natural ligand and lack of a monoclonal antibody against murine CD7, the in vivo functions of CD7 have until recently remained obscure. Recent studies in CD7-deficient mice have provided new insights into CD7 function, and demonstrated key roles for CD7 in regulating peripheral T and NK cell cytokine production and sensitivity to LPS-induced shock syndromes. This article reviews recent work on the expression, structure, and function of CD7, and discusses roles the CD7 molecule might play in T and NK cell development and function.
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PMID:Structure and function of the CD7 molecule. 1053 Apr 32

Sezary cell leukemia (SCL) is a rare T cell neoplasia that has been suggested to be a variant of T-prolymphocytic leukemia (T-PLL). Both disorders have an aggressive clinical course, lymphocytosis with characteristic morphology, lymphadenopathy, hepatomegaly, characteristic cytogenetic abnormalities and mature T cell phenotypes. Skin lesions, however, are mainly found in T-PLL. We describe a patient with T-PLL/SCL, who atypically presented with severe seropositive polyarthritis and skin lesions, responding to treatment with human CD52 antibody, CAMPATH-1H and pentostatin. Meningeal leukemia and an assumed myocardial infiltration subsequently developed. Polyarthritis is common in T large granular lymphocyte leukemia and adult T cell lymphoma-leukemia, but both entities could be ruled out in the present case. In rheumatoid arthritis, an expansion of CD4+ and/or CD8+ T lymphocytes is well documented and this phenomenon is believed to be of pathogenetic importance. We speculate that the T cell clone in the present case had special homing properties or cytokine effects resulting in synovitis.
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PMID:Seropositive polyarthritis and skin manifestations in T-prolymphocytic leukemia/Sezary cell leukemia variant. 1075 96

In a series of 24 patients with chronic T-lymphoid disorders [13 T-prolymphocytic leukaemia (T-PLL) and 11 Sezary syndrome] we have studied (i) chromosome 17p abnormalities and p53 allele deletion by fluorescence in situ hybridization; (ii) mutation in the exons of the p53 gene by direct DNA sequencing; and (iii) p53 protein expression by immunocytochemistry and, in some cases, also by flow cytometry with DO-1, a monoclonal antibody to the p53 protein. The study revealed p53 deletion and accumulation of p53 protein in the absence of mutation in the exons that included the hot-spots and differs from that described in B-prolymphocytic leukaemia. Seven T-PLL and five Sezary syndrome patients had p53 overexpression, and five T-PLL and nine Sezary syndrome patients showed p53 deletion. Although the majority of cases with p53 accumulation had p53 deletion, the proportion of cells with the deletion did not correlate with the proportion of cells positive for p53 expression. Two cases of T-PLL showed strong p53 expression in the absence of p53 deletion, and one case of Sezary syndrome with p53 deletion in 97% of cells did not express p53. These findings suggest that a non-mutational mechanism exists for the accumulation of p53 protein in these T-cell disorders. The oncogenic effect of the accumulating wild-type protein has been reported in other malignancies. Whether haploidy resulting from p53 deletion contributes to this mechanism has yet to be determined. Alternatively, the frequent loss of the p53 gene could be associated with the deletion of an adjacent gene, which could be involved in the pathogenesis of these diseases.
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PMID:p53 allele deletion and protein accumulation occurs in the absence of p53 gene mutation in T-prolymphocytic leukaemia and Sezary syndrome. 1093 Sep 96

Interleukin-2 (IL-2) is a growth factor which upon binding to high-affinity receptors (IL-2Ralphabetagamma) triggers mitogenesis in T cells. IL-2Ralpha expression is restricted to T cells which have recently encountered antigen, and in healthy individuals the majority (>95%) of peripheral T cells are IL-2Ralpha negative. An aberrant expression of IL-2Ralpha has recently been described in cutaneous T-cell lymphoma (CTCL). Here, we study the regulation of IL-2Ralpha expression and STATs in a tumor cell line obtained from peripheral blood from a patient with Sezary syndrome (SS), a leukemic variant of CTCL. We show that (1) STAT3 (a transcription factor known to regulate IL-2Ralpha transcription) is constitutively tyrosine-phosphorylated in SS tumor cells, but not in non-malignant T cells; (2) STAT3 binds constitutively to a STAT-binding sequence in the promotor of the IL-2Ralpha gene; (3) the Janus kinase inhibitor, tyrphostine AG490, inhibits STAT3 activation, STAT3 DNA binding, and IL-2Ralpha mRNA and protein expression in parallel; and (4) tyrphostine AG490 inhibits IL-2 driven mitogenesis and triggers apoptosis in SS tumor cells. In conclusion, we provide the first example of a constitutive STAT3 activation in SS tumor cells. Moreover, our findings suggest that STAT3 activation might play an important role in the constitutive IL-2Ralpha expression, survival, and growth of malignant SS cells.
Leukemia 2001 May
PMID:Constitutive STAT3-activation in Sezary syndrome: tyrphostin AG490 inhibits STAT3-activation, interleukin-2 receptor expression and growth of leukemic Sezary cells. 1136 40

SHP-1 is a key tyrosine phosphatase that acts as a negative regulator of signal transduction in lymphocytes, which has been found down-regulated in several T cell lines derived from human T cell malignancies. The standardization of a sensitive ELISA for the quantification of SHP-1 protein in peripheral T and B lymphocytes has enabled us to quantify the SHP-1 content of freshly isolated T cells from patients with Sezary syndrome and in the Sezary T cell line HUT-78. In all cases, a dramatic decrease in the content of this protein, when compared with the content in healthy volunteer controls, was observed. These results were corroborated when the expression of SHP-1 mRNA was analyzed. In order to study whether there was any correlation between SHP-1 protein expression and tyrosine phosphorylated state of JAK3, the state of phosphorylation of JAK3 was studied in the T cell line HUT-78, and found to be highly phosphorylated. These results suggest that SHP-1 might be involved in maintaining the IL-2R/JAK3 signaling pathway under control and point towards a role of SHP-1 in the pathogenesis of the disease.
Leukemia 2002 Aug
PMID:SHP-1 expression in peripheral T cells from patients with Sezary syndrome and in the T cell line HUT-78: implications in JAK3-mediated signaling. 1214 87

The most common variant of cutaneous T-cell lymphomas (CTCLs) is mycosis fungoides (MF), a malignant proliferation of atypical CD4+ CD45Ro+ T-cells that initially proliferate in the skin and later invades lymph nodes and other organs including the blood (Sezary syndrome). The pathogenesis of CTCL is largely unknown. We present definitive data showing a correlation between degree and prevalence of hypomagnesemia and hypocalcemia and clinical stage of MF. Hypomagnesemia was present in 22.2% of MF patients with early stage (n = 27), 38.5% of intermediate stage (n = 13), and 67.5% of advanced stage disease (n = 40). Hypocalcemia was present in 8.3% of MF patients with early stage (n = 24), 54.5% with intermediate stage (n = 11), and 61.0% with advanced stage disease (n = 41). The odds ratios for having hypomagnesemia and hypocalcemia in patients with stage II or higher MF compared with stage I patients were 5.33 and 16.24, respectively. Hypomagnesemia has been associated with immune function abnormalities including the development of T-cell leukemia-lymphoma in rats. We hypothesize that the hypomagnesemia may play a role in the progression or pathogenesis of MF or the Sezary syndrome (SS). This retrospective case series is the first study ever to report a relationship between serum cations and CTCL in humans.
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PMID:Hypomagnesemia and hypocalcemia in mycosis fungoides: a retrospective case series. 1215 99

The current World Health Organization (WHO) classification of hematopoietic malignancies defines several types of mature T-cell leukemia including T-cell prolymphocytic leukemia (T-PLL), Sezary syndrome (SS), and T-cell large granular lymphocytic (T-LGL) leukemia. These neoplasms can show overlapping features with each other and with T-cell lymphomas involving peripheral blood (PB). We analyzed the spectrum of clinicopatho-logic features in 102 mature T-cell leukemias and compared them to 10 hepatosplenic T-cell lymphomas that involved PB. T-PLL, defined as a T-cell leukemia showing rapidly rising PB lymphocyte counts, was the only tumor type expressing the oncoprotein TCL1 (71% of cases) and could present with relatively low lymphocyte levels or small tumor cell morphology. SS, defined by accompanying erythrodermic skin disease, was frequently associated with peripheral eosinophilia but could also develop high numbers of prolymphocytes, especially late in the disease course. T-LGL leukemia, defined by accompanying cytopenias or autoimmune phenomena (or both), had the best clinical outcome and generally showed the lowest circulating lymphocyte levels with only a few cases developing marked lymphocytosis. Using the dominant clinical or phenotypic feature, we describe here the degree of overlap among currently recognized WHO categories and identify areas where further clarification is needed. Our results indicate that incorporation of additional criteria, such as TCL1 expression status and hematologic parameters, can assist in a more accurate classification.
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PMID:A systematic approach to diagnosis of mature T-cell leukemias reveals heterogeneity among WHO categories. 1549 62

T-cell prolymphocytic leukemia (T-PLL) can involve extramedullary sites, but the diagnosis is usually established by examination of blood and bone marrow. As a result, the histologic findings at extramedullary sites are poorly documented in the literature. We describe 19 extramedullary biopsy specimens from 14 patients with T-PLL. Skin (n = 10) was the most common site biopsied. T-PLL surrounded dermal blood vessels and appendages (n = 6), diffusely replaced dermis (n = 3), or formed a subcutaneous mass (n = 1). Other extramedullary sites included liver and lymph nodes (3 each) and spleen, lung, and cecum (1 each). In liver and lymph nodes, the neoplasm predominantly involved portal tracts and paracortex, respectively. Cytologically, the T-PLL cells were round (n = 16) or Sezary cell-like (n = 3). Nucleoli were observed in a subset of cells in 8 specimens and were prominent in 3 specimens. Immunostaining for T-cell leukemia-1 (TCL-1) was positive in specimens from 9 (64%) of 14 patients. We conclude that the prolymphocytoid features of T-PLL cells can be difficult to detect in routinely stained sections of extramedullary biopsy specimens. TCL-1 expression can aid in diagnosis at extramedullary sites.
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PMID:T-cell prolymphocytic leukemia involving extramedullary sites. 1571 43

Avicins are plant-derived triterpenoid stress metabolites that have both proapoptotic and cytoprotective properties. Avicins induce apoptosis in Jurkat T leukemia cells by targeting mitochondria and release of cytochrome c that occurs in a p53-independent manner. However, postmitochondrial antiapoptotic barriers, such as increased expression of heat shock proteins (Hsp) and X-linked inhibitor of apoptosis proteins (XIAP), frequently exist in cancer cells and often account for resistance to chemotherapy and a poor prognosis. In this article, we show the role of avicins in the activation of stress-regulated ubiquitination and degradation of Hsp70 and XIAP. This is the first report showing the regulation of Hsp70 via the ubiquitin/proteasome pathway. We also show the induction of E3alpha ubiquitin ligase in avicin-treated Jurkat T leukemia cells, and its involvement in the degradation of XIAP. Avicin-mediated suppression of Hsp70 and XIAP was further confirmed in other leukemic/lymphoma cell lines and freshly isolated peripheral blood lymphocytes from Sezary syndrome patients. No change in the Hsp70 and XIAP proteins was observed in peripheral blood lymphocytes from normal donors. We propose that the ability of avicins to induce ubiquitination and regulate the degradation of Hsp70 and XIAP in leukemia cells could have important implications in the treatment of drug-resistant neoplasia and inflammatory disorders.
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PMID:Triterpenoid electrophiles (avicins) suppress heat shock protein-70 and x-linked inhibitor of apoptosis proteins in malignant cells by activation of ubiquitin machinery: implications for proapoptotic activity. 1575 21

The Sezary's syndrome is a lymphoproliferative disorder from the group of chronical lymphocytic leukaemia originated from the T-cell lineage. Authors are presenting the patient with Sezary's syndrome for the first time ever diagnosed in the Institute of Haematology. The patient, 58 years old got ill in summer 1989. with the symptoms of strong itch and erythematous papullas over the sin. In April 1990. he came to the Institute of Hematology where he was diagnosed as a Sezary's syndrome case on the evidence of generalized erythrodermia, identification of lymphocytes with cerebriform nucleus in peripheral blood and membrane-marker analysis that showed aberant post-thymic proliferation of T-lymphocytes in bone marrow. The patient wastreated with a polychemiotherapy and with "electron beam" therapy with temporary improvement, but died in January 1991 with sepsis and a hepathorenal syndrome.
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PMID:[Sezary's syndrome (case report)]. 1629 36


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