Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine children with mediastinal non-Hodgkin's lymphoma (NHL) were treated according to our new regimen which is characterized by intensified therapy with high-dose cytosine arabinoside (HDCA). After induction therapy with a combination of five drugs, such as vincristine, doxorubicin, cyclophosphamide, 1-asparaginase, and prednisolone, intermediate dosages of methotrexate (MTX) (1 g/m2) and HDCA (1.5 g/m2 x 12 doses) were administered. All but one patient (88.9%) achieved complete remission and then received this intensified therapy. With a median follow-up period of 25.5 months, five patients are still in complete remission, but three patients have relapsed. From the phenotypic point of view, these relapsed patients showed only very immature T-cell differentiation antigens such as CD2 and CD7 (or CD5). These results suggest that HDCA as intensified therapy for children with mediastinal NHL seems to be effective. However, for patients with an immature phenotype of T-lineage cells, more sophisticated regimens should be prepared.
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PMID:Poor prognosis of mediastinal non-Hodgkin's lymphoma with an immature phenotype of CD2+, CD7 (or CD5)+, CD3-, CD4-, and CD8-. 278 59

We describe the clinical and laboratory features of an unusual case with Sezary cell-like leukemia. Clinical manifestations were: anemia (Hb 9.4 g/dl), severe thrombocytopenia (5 x 10(9)/l), lymphocytosis (43 x 10(9)/l) and splenomegaly. There was no lymphadenopathy, hepatomegaly or skin lesions. Bone marrow trephine showed diffuse infiltration by atypical lymphoid cells. By ultrastructural analysis the cells were small to medium-size lymphocytes with nuclear features identical to Sezary cells. Immunophenotyping showed that most peripheral blood mononuclear cells were negative with B lymphoid, myeloid, and stem cell-associated markers and were also negative with most T lymphoid markers (CD2, CD4, membrane/cytoplasmic CD3, CD5 and CD8). However, they were positive with CD38 (70%), CD7 (25%) and TIA-2 (25%). Molecular analysis showed a clonal rearrangement of the TCR beta and gamma chain genes. The patient was initially treated with vincristine, doxorubicin and asparaginase and then with six cycles of CHOP, achieving a complete remission and remaining free of disease 22 months from diagnosis. Aberrant immunophenotypes are not frequent in primary T cell leukemias. This is the first case of a rare type of T cell neoplasm, Sezary cell-like leukemia, in which cells lacked most of the T cell-associated antigens.
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PMID:Sezary cell-like leukemia with atypical immunophenotype. 926 98

Natural killer (NK) cells are lymphocytes with large granular lymphocyte morphology, CD3-CD56+ phenotype, non-MHC-restricted cytotoxicity, and germ-line configuration T-cell receptor genes. Two types of lymphomas originating from NK cells have been described; blastic NK-cell lymphoma, and nasal-type NK-cell lymphoma. Because recent reports indicate that blastic NK-cell lymphoma originates from the precursors of plasmacytoid dendritic cells, I will focus mainly on nasal-type NK-cell lymphoma, and discuss its pathogenesis, diagnostic problems, treatment strategy, and outcome. Nasal-type NK-cell lymphoma develops mostly in the nasal cavity and rarely in other sites, such as the skin and intestinal tract. Epstein-Barr virus (EBV) is found in lymphoma cells of almost all the patients, and is considered to be the etiologic agent. Indeed, EBV easily infects NK cells in the absence of CD21 antigen, or EBV receptor, on the surface of NK cells. Further, various types of oncogenes and suppressor oncogenes are found to be involved in its pathogenesis. Based on the data obtained from paraffin-embedded specimens, it is difficult to determine whether the lymphoma cells are of T-cell or NK-cell lineage, because immunohistochemical staining of cytoplasmic CD3 is positive both in T and NK cells, and CD56 is positive in a part of T cells. The presence of CD5 antigen indicates T-cell lineage. When the disease is limited, radiation therapy is effective, but not satisfactory. A new trial to use simultaneously both radiation and chemotherapy has started in Japan. In advanced stages, a combination chemotherapy including L-asparaginase seems to be promising, and high-dose chemotherapy with autologous or allogeneic stem cell support is under investigation. A recent report described the expression of short-length P-glycoprotein (P-gp), but not full-length P-gp in NK cells, and this mini-P-gp is unable to extrude daunorubicin. These findings may change the treatment strategy. Finally, I will present the results on interim analysis of 166 cases of nasal-type NK-cell lymphoma collected in Japan between 1994 and 1998.
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PMID:NK cell lymphoma. 1243 Sep 11

Blastic NK cell lymphoma/leukemia is a rare and highly malignant neoplasia in both adults and children. It is characterized by lymphoblastoid morphology without cytoplasmic granules and immature NK cell immunophenotypes (CD56+, CD57-, CD16-). It has predilection for extranodal organ involvement, and the prognosis of affected patients is extremely poor under the current chemotherapy. We present a 14-year-old girl who was diagnosed as having blastic NK cell leukemia with mediastinal, pleural, and pericardial involvement. Immunophenotyping of her leukemic cells showed positive for CD2, CD5, CD7, CD34, CD56, HLA-DR, and cytoplasmic CD3. T cell receptor (TCR) and Immunoglobulin heavy chain genes were not rearranged. She received chemotherapy for acute lymphoblastic leukemia incorporating L-asparaginase (L-asp) which successfully induced complete remission. Bone marrow transplantation (BMT) from her HLA-identical sibling was conducted after two courses of consolidation therapy. Expression of aspargine synthetase (AS) protein in the leukemic cells at diagnosis was examined by an immunocytochemical method. She remains in hematological remission for over 36 months after BMT. The expression of AS protein was negative, suggesting that the leukemic cells were sensitive to L-asp. Induction and consolidation therapy incorporating L-asp followed by allo-BMT might be a promising treatment for child hood blastic NK cell leukemia, but more samples of the rare leukemia need to be studied before any definitive conclusions can be drawn.
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PMID:Childhood blastic NK cell leukemia successfully treated with L-asparagenase and allogeneic bone marrow transplantation. 1512 19

The significant difference between biological properties of L-lysine-alpha-oxidase from Trichoderma harzianum Rifai (LO) and L-asparaginase from E. coli has been observed in vitro and in vivo. High antitumor activity was shown against 8 types of murine and rat transplanted tumors with a wide range of LO therapeutic doses: 35-350 U/mg. The LO conjugates with monoclonal antibodies CD5 specific to the surface of cell line Yurkat were obtained without significant loss of either enzymatic and cytotoxic activity or immunological specificity. The further perspective investigation for the clinical application of the native or conjugated enzymes is discussed.
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PMID:[Biological properties of L-lysine alpha-oxidase in native and conjugated form]. 1551 84

A 31-year-old man underwent kidney transplantation in 1996, and had been on immunosuppressants. In 2005, he presented with discomfort on swallowing. Swelling of the left tonsil and a mediastinal mass were observed. A biopsy of the left tonsil showed a monotonous proliferation of atypical lymphocytes suggesting post-transplant lymphoproliferative disorder (PTLD). The reduction of immunosuppressants did not result in any clinical improvements, and he developed bilateral cervical lymphadenopathy. A biopsy of the cervical lymph node also showed monotonous proliferation of TdT, CD3, CD5, CD7, CD10, and CD34-positive immature cells. T-cell receptor rearrangement, but not EBER, was detected. Based on these findings, monomorphic T-cell PTLD was diagnosed. He was treated with four different chemotherapeutic regimens without any clinical improvements, and the PTLD became leukemic. Chemotherapy consisting of L-asparaginase, vincristine, and dexamethasone (LVD) was then given, which resulted in massive tumor lysis. However, after two courses of LVD, complete remission was achieved. T-cell PTLD is a rare disorder, characterized by its refractoriness to chemotherapy as opposed to B-cell PTLD. Our experience suggests that L-asparaginase-based chemotherapy may improve the prognosis of T-cell PTLD.
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PMID:[Successful treatment with L-asparaginase-based combination chemotherapy for refractory T-cell post-transplant lymphoproliferative disorder]. 1751 21

Primary cutaneous T-cell lymphomas are rare and can be difficult to classify precisely. We present a case of extranodal natural killer (NK)/T-cell lymphoma in a previously healthy, immunocompetent man who presented with extensive necrotic leg ulcers and disseminated skin nodules. Immunohistochemical studies revealed that the tumour cells were positive for CD3, CD30, granzyme B and T-cell intracellular antigen-1, and negative for CD5 and CD56, with positive staining for Epstein-Barr virus (EBV) RNA on in situ hybridization. A diagnosis of extranodal NK/T-cell lymphoma was made, based on the presence of cytotoxic granules and positive EBV RNA staining. The patient was treated with a regimen of chemotherapy comprising corticosteroids, intravenous methotrexate, ifosphamide, L-asparaginase and etoposide with initial response.
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PMID:Nasal-type extranodal natural killer/T-cell lymphoma presenting with extensive leg ulcers. 2005 38