The gastric marginal zone B-cell lymphoma of MALT type.

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摘要：

Megaloblastic anemia 1 (MGA1) is an autosomal recessive disorder caused by the selective intestinal malabsorption of intrinsic factor (IF) and vitamin B-12/cobalamin (Cbl) in complex. Most Finnish patients with MGA1 carry the disease-specific P1297L mutation (FM1) in the IF-B-12 receptor, cubilin, By site-directed mutagenesis, mammalian expression, and functional comparison of the purified wild-type and FM1 mutant forms of the If-Cbl-binding cubilin region (CUB domains 5-8, amino acid 928-1386), we have investigated the functional implications of the P1297L mutation. Surface plasmon resonance analysis revealed that the P1297L substitution specifically increases the K-d for IF-Cbl binding several-fold, largely by decreasing the association rate constant. In agreement with the binding data, the wild-type protein, but not the FM1 mutant protein, potently inhibits 37 degrees C uptake of iodine 125-IF-Cbl in cubilin-expressing epithelial cells. In conclusion, the data presented show a substantial loss in affinity of the FM1 mutant form of the IF-Cbl binding region of cubilin, This now explains the malabsorption of Cbl and Cbl-dependent anemia in MGA1 patients with the FM1 mutation. (C) 2000 by The American Society of Hematology.

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关键词：

Humans Gastric Mucosa Helicobacter pylori Antineoplastic Agents Treatment Outcome Immunophenotyping Mutation Lymphoma, B-Cell, Marginal Zone Stomach Neoplasms