Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 16-year-old girl who had been treated for B-precursor acute lymphoblastic leukemia (ALL) presented with a mass in the left orbit as an isolated relapse. Five years earlier, she had undergone chemotherapy that promptly resulted in a complete remission. For prophylaxis of central nervons system leukemia, the patient received cranial radiotherapy (18 Gy) with shielding of the orbit and 15 cycles of intrathecal MTX and prednisolone. Cerebrospinal fluid analysis did not detect infiltration during the treatment course. Exophthalmos of the eft eye and hyperemia of the conjuctiva developed 15 months after therapy. Computed tomography showed a retro-orbital mass behind the left eye. Though bone marrow aspiration was negative, biopsy specimens from the mass disclosed the infiltration of CD10-positive leukemic blasts. After 8 courses of chemotherapy, 5 cycles of intrathecal MTX, and orbital irradiation (24 Gy), the mass disappeared. All relapse as an isolated retro-orbital mass is very rare, and only 3 cases have been reported to date.
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PMID:[Relapse of acute lymphoblastic leukemia as a retro-orbital mass]. 1062 31

Methotrexate (MTX) is an antifolate that is widely used for the treatment of childhood acute lymphoblastic leukemia (ALL) and a number of other malignant and nonmalignant diseases. Within cells, MTX is metabolized to more active methotrexate polyglutamates (MTXPG), and these polyglutamates are subsequently cleaved in lysosomes by gamma-glutamyl hydrolase (GGH). GGH is reported to act as either an endopeptidase or an exopeptidase, exhibiting species differences in these functions. To better define the in vivo functions of GGH in human leukemia cells, we characterized GGH activity with different MTXPG substrates (MTX with three to five glutamates) in human T- and B-lineage leukemia cell lines, and in primary leukemia cells from newly diagnosed patients with ALL. Parameters estimated from fitting a series of hypothetical mathematical models to the data revealed that the experimental data were best fit by a model where GGH simultaneously cleaved multiple glutamyl residues, with highest activity at cleaving the outermost or two outermost residues from a polyglutamate chain. The model also revealed that GGH has a higher affinity for longer chain polyglutamates. Together, these findings provide new insights to the intracellular disposition of MTX in human ALL cells, and provides a mechanism-based model for characterizing differences among patients and genetic subtypes of ALL.
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PMID:Methotrexate intracellular disposition in acute lymphoblastic leukemia: a mathematical model of gamma-glutamyl hydrolase activity. 1211 48

Primary central nervous system lymphoma (PCNSL) has been immunohistochemically classified into two subtypes, germinal center (GC) B-cell and non-GC B-cell, but the prognostic impact of these subtypes remains debated. We investigated clinical features and prognostic significance of immunohistochemical subtypes that were identified by expression patterns of three B-cell differentiation markers in PCNSL. We also analyzed a factor related to responsiveness to high-dose methotrexate (HD-MTX) chemotherapy. Tumors from 32 PCNSL patients were immunohistochemically evaluated for expression of cluster of differentiation (CD) 10, B-cell lymphoma-6 (BCL-6), and multiple myeloma oncogene-1 (MUM-1) and classified into subtypes according to the expression patterns of these markers. Clinical features and prognostic outcome of these subtypes were investigated. Twenty-three patients were treated with HD-MTX-based chemotherapy followed by whole-brain radiation therapy (WBRT), and nine were treated with WBRT alone. Three immunohistochemical subtypes were identified, including A-type expressing CD10, BCL-6, and MUM-1 (12 patients), B-type expressing BCL-6 and MUM-1 (12 patients) and C-type expressing MUM-1 only (8 patients). Response rate in the HD-MTX therapy group was 57.1% (4/7) in A-type, 87.5% (7/8) in B-type, and 75% (6/8) in C-type. C-type with the lowest metabolic activity showed significantly longer overall survival than A-type with the higher uptake of methionine (71.6 versus 39.6 months) (P<0.05). Immunohistochemical identification of PCNSL based on the B-cell differentiation stage revealed three types of tumors, showing different metabolic activity and survival time. Refined immunohistochemical classification of PCNSL subtypes may become a useful tool for predicting more accurate prognosis and accessing sensitivity to HD-MTX therapy.
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PMID:Prognostic significance of immunohistochemical subtypes based on the stage of B-cell differentiation in primary CNS lymphoma. 3193 63

A 58-year-old Japanese woman complained of a painful right maxillary premolar gingiva and ulcer. The patient had RA and had been treated with several immunosuppressive drugs such as methotrexate. Head and neck CT indicated no obvious bone destruction with maxillary. However, chest CT indicated the presence of nodular mass of the bilateral lungs. FDG-PET/CT indicated the presence of increased uptake in both lesions. On immunohistochemistry, atypical large-sized lymphocytes were positive for CD20 and EBER-ISH and negative for CD3, CD5, and CD10; the Ki-67 labeling index was high, the histopathological diagnosis was EBV-positive DLBCL, and the clinical diagnosis was MTX-LPD. The patient's treatment with MTX was then discontinued; we removed the alveolar bone which necrosed after 5 weeks. The lesion and the nodular mass at the bilateral lungs had completely disappeared after 7 weeks.
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PMID:Methotrexate-Associated Lymphoproliferative Disorder Developed Ectopically in the Maxillary Gingiva and Bilateral Lungs. 3241 Dec 53