Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An indirect platelet radioactive antiglobulin test (PRAT) was used to evaluate serum antiplatelet antibody and complement activation in 114 patients with lymphoproliferative disease. Overall, 60% of serum samples gave a positive indirect PRAT. Positive PRAT was observed in 85% of patients with chronic lymphocytic leukemia (CLL) and megakaryocytic thrombocytopenia, as well as in about half the patients with CLL and a normal platelet count or amegakaryocytic thrombocytopenia. In contrast to findings in patients with idiopathic autoimmune thrombocytopenic purpura or in those with leukemia who were alloimmunized, positive PRAT in patients with lymphoproliferative disease was predominantly caused by C3-only sensitization of platelets. Results were analyzed in relation to other clinical and laboratory findings. There was no significant difference in antiglobulin sensitization pattern between CLL and other lymphomas, different cell type, stage of disease, presence or absence of splenomegaly, recent or distant chemotherapy, sex, or history of pregnancy. Previous transfusion did affect antiglobulin sensitization patterns, as did presence of autoimmune hemolytic anemia. A high frequency of low serum complements (CH50, C3, C4, and factor B) and increased circulating immune complexes was observed; these did not correlate with frequency or sensitization pattern of positive PRAT. Amounts of bound anti-C3 and anti-IgG were significantly higher in patients with lymphoproliferative disease and positive antiglobulin test than in normal individuals; there was, however, no correlation between amount of antiglobulin serum bound and platelet counts. There was an 87% correlation in direct and indirect PRAT in 24 patients tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indirect platelet radioactive antiglobulin test in patients with lymphoproliferative disease. 394 93

The R98S mutation in ribosomal protein L10 (RPL10 R98S) affects 8% of pediatric T-cell acute lymphoblastic leukemia (T-ALL) cases, and was previously described to impair cellular proliferation. The current study reveals that RPL10 R98S cells accumulate reactive oxygen species which promotes mitochondrial dysfunction and reduced ATP levels, causing the proliferation defect. RPL10 R98S mutant leukemia cells can survive high oxidative stress levels via a specific increase of IRES-mediated translation of the anti-apoptotic factor B-cell lymphoma 2 (BCL-2), mediating BCL-2 protein overexpression. RPL10 R98S selective sensitivity to the clinically available Bcl-2 inhibitor Venetoclax (ABT-199) was supported by suppression of splenomegaly and the absence of human leukemia cells in the blood of T-ALL xenografted mice. These results shed new light on the oncogenic function of ribosomal mutations in cancer, provide a novel mechanism for BCL-2 upregulation in leukemia, and highlight BCL-2 inhibition as a novel therapeutic opportunity in RPL10 R98S defective T-ALL.
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PMID:The ribosomal RPL10 R98S mutation drives IRES-dependent BCL-2 translation in T-ALL. 3085 Jul 35