Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report here the clinical and cytogenetic findings in a 3-year-old girl with pre-B-cell acute lymphoblastic leukemia presenting as a primary tumor of bone. A unique translocation t(7;15)(q22;q14-15) is described.
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PMID:A unique chromosome translocation, t(7;15), in a pediatric patient with pre-B-cell lymphoma presenting as a primary tumor of bone. 320 12

We describe 9 cases of precursor B-cell lymphoblastic lymphoma (LYL) without evidence of marrow or blood involvement. Four patients had superficial nodal disease, 2 cutaneous involvement, and 1 each ovarian, retroperitoneal, or tonsillar primary tumor. Six patients had limited disease; 3 patients were stage III. Immunophenotyping revealed a terminal deoxynucleotidyl transferase (TdT)-positive, immature B-cell population with variable expression of CD10, CD20, and CD45. All patients are in complete clinical remission (median follow-up, 14 months). A literature review yielded 105 patients with a diagnosis of precursor B-cell LYL based on less than 25% marrow involvement. Of these, 64% were younger than 18 years. Skin, lymph nodes, and bone were the most common sites of disease. Mediastinal involvement was uncommon. TdT, CD19, CD79a, CD10, and HLA-DR were the most frequently expressed antigens, while CD45 and CD20 were expressed in only two thirds of the cases. Cytogenetic analysis showed additional 21q material as a recurring karyotypic abnormality. At a median follow-up of 26 months, 74% of patients were alive; the median survival was 19 months for patients dying of disease. Comparison with precursor B-cell acute lymphoblastic leukemia showed several overlapping features, although distinct differences were identified.
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PMID:Precursor B-cell lymphoblastic lymphoma. A study of nine cases lacking blood and bone marrow involvement and review of the literature. 1139 84

Previous studies have shown that the interleukin-12 receptor beta2 (IL-12Rbeta2) gene is expressed in normal naive, germinal center and memory B cells but not in their malignant counterparts. The aim of this study was to investigate (i) whether the IL-12Rbeta2 gene is silenced in B-cell acute lymphoblastic leukemia (B-ALL) cells, and (ii) what the functional implications of such silencing for tumor growth are. Here, we show that although mature B cells expressed both chains of the IL-12R, normal pro-B and pre-B cells failed to express the IL-12Rbeta2 chain. Similarly, primary tumor cells from pediatric pro-B, early pre-B, and pre-B ALL (30 cases) did not express the IL-12Rbeta2 chain. IL-12Rbeta2 gene silencing in B-ALL was found to depend on methylation of a CpG island in exon 1. Such methylation was not detected in normal early B cells that when differentiated into mature B cells expressed the IL-12Rbeta2 gene. Detection of IL-12Rbeta2 mRNA and protein in the tumorigenic 697 pre-B-ALL cell line allowed to perform functional experiments in severe combined immunodeficient/nonobese diabetic mice receiving 697 cells with or without human recombinant IL-12 (hrIL-12). hrIL-12 administration reduced tumor growth and metastasis through antiproliferative and proapoptotic rather than antiangiogenic, activities. In conclusion, epigenetic silencing of the IL-12Rbeta2 gene represents a novel mechanism of tumor escape for B-ALL cells.
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PMID:Methylation of the IL-12Rbeta2 gene as novel tumor escape mechanism for pediatric B-acute lymphoblastic leukemia cells. 1661 14

Genomic studies have identified recurrent somatic mutations in acute leukemias. However, current murine models do not sufficiently encompass the genomic complexity of human leukemias. To develop preclinical models, we transplanted 160 samples from patients with acute leukemia (acute myeloid leukemia, mixed lineage leukemia, B-cell acute lymphoblastic leukemia, T-cell ALL) into immunodeficient mice. Of these, 119 engrafted with expected immunophenotype. Targeted sequencing of 374 genes and 265 frequently rearranged RNAs detected recurrent and novel genetic lesions in 48 paired primary tumor (PT) and patient-derived xenotransplant (PDX) samples. Overall, the frequencies of 274 somatic variant alleles correlated between PT and PDX samples, although the data were highly variable for variant alleles present at 0-10%. Seventeen percent of variant alleles were detected in either PT or PDX samples only. Based on variant allele frequency changes, 24 PT-PDX pairs were classified as concordant while the other 24 pairs showed various degree of clonal discordance. There was no correlation of clonal concordance with clinical parameters of diseases. Significantly more bone marrow samples than peripheral blood samples engrafted discordantly. These data demonstrate the utility of developing PDX banks for modeling human leukemia, and emphasize the importance of genomic profiling of PDX and patient samples to ensure concordance before performing mechanistic or therapeutic studies.
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PMID:Patient-derived xenotransplants can recapitulate the genetic driver landscape of acute leukemias. 2736 83