Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In classical Hodgkin lymphoma (cHL) the mechanisms underlying primary refractory disease and relapse remain unknown. To gain further insight into cHL pathogenesis and genomic changes linked to treatment response, we studied 53 cHL patients by array comparative genomic hybridization, including 23 patients whose primary treatment failed, using DNA from microdissected HRS cells. Copy number alterations found in more than 20% of cases included gains of 2p, 9p, 16p, 17q, 19q, 20q, and losses of 6q, 11q, and 13q. We identified at high resolution recurrent changes defining minimally gained and lost regions harboring genes involved in nuclear factor kappaB signaling, such as REL, IKBKB, CD40, and MAP3K14. Gains of chromosome 16p11.2-13.3 were significantly more frequent in pretreatment and relapse biopsies of unresponsive patients and were associated with shortened disease-specific survival (P = .028). In the therapy-resistant HL cell line KMH2, we found genomic gains and overexpression of the multidrug resistance gene ABCC1 mapping to cytoband 16p13.11. We show that doxorubicin exposure to KMH2 induces ABCC1 expression and that siRNA silencing of ABCC1 sensitizes KMH2 cells to doxorubicin toxicity in vitro, suggesting that overexpression of ABCC1 contributes to the drug resistance phenotype found in KMH2.
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PMID:Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome. 2065 Oct 79

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with unclear pathogenesis. DLBCL accounts for 30%-35% of all non-Hodgkin lymphomas (NHLs) and is an aggressive subtype of mature B-cell neoplasm. At present, half of DLBCL cases can be cured, although one-third of patients experience recurrence after treatment and enter advanced tumor stage. This study aimed to investigate the differentially expressed proteins in activated B-cell-like-DLBCL (ABC-DLBCL) through quantitative proteomics (iTRAQ). Seven ABC-DLBCL experimental samples and eight control samples (reactive hyperplasia of the lymph node) were obtained from fresh tissues. The exclusion criteria were expressed as follows: (1) patients with other lymphoid diseases; and (2) patients undergoing chemical treatment. A total of 5974 proteins were identified. P value < 0.05 and multiple expressions were more than 1.2-fold. A total of 131 upregulated and 204 downregulated differentially expressed proteins were identified. Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) network analysis was conducted. The expression levels of HSP90AB1, GNA13, LAMB2, LAMA5, YWHAZ, and IKBKB were evaluated through PRM and TCGA to validate the accuracy of iTRAQ and liquid chromatography-tandem mass spectrometry results. Results of differential multiple and t-test showed differences in the expression levels of six target proteins between the control and experimental groups. To the best of our knowledge, the present study is the first to identify proteins associated with ABC-DLBCL using iTRAQ technology. Our results provide new insights into the pathogenesis of ABC-DLBCL. The combination of ABC-DLBCL-associated signaling pathway proteins and targeted therapy to reverse drug resistance is of great significance in improving the comprehensive treatment of lymphoma and reducing mortality of affected individuals. The feasibility of the present study is limited due to the number of samples, and future studies are required to determine the function of proteins in ABC-DLBCL development.
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PMID:Quantitative proteomics analysis of differentially expressed proteins in activated B-cell-like diffuse large B-cell lymphoma using quantitative proteomics. 3132 89

The mutational landscape of grey zone lymphoma (GZL) has not yet been established and differences to related entities are largely unknown. Here, we studied coding sequence mutations of 50 EBV-negative GZL and 20 polymorphic EBV-positive DLBCL NOS (poly-EBV-L) in comparison to classical Hodgkin lymphoma (cHL), primary mediastinal large B cell lymphoma (PMBCL), and diffuse large B cell lymphoma (DLBCL). Exomes of 21 GZL and 7 poly-EBV-L cases along with paired normals were analyzed as a discovery cohort followed by targeted sequencing of 217 genes in an extension cohort of 29 GZL and 13 poly-EBV-L cases. GZL cases with thymic niche involvement (anterior mediastinal mass) displayed a mutation profile closely resembling cHL and PMBCL, with SOCS1 (45%), B2M (45%), TNFAIP3 (35%), GNA13 (35%), LRRN3 (32%) and NFKBIA (29%) being the most recurrently mutated genes. In contrast, GZL cases without thymic niche involvement (N=18) had a significantly distinct pattern, enriched in mutations related to apoptosis defects (TP53 (39%), BCL2 (28%), BIRC6 (22%)) and depleted in GNA13, XPO1or NFKB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA). They also presented more BCL2/BCL6 rearrangements as opposed to thymic GZL. Poly-EBV-L cases presented a distinct mutational profile including STAT3 mutations and a significantly lower coding-mutation load in comparison to EBV-negative GZL. Our study highlights characteristic mutational patterns in GZL associated with presentation in the thymic niche suggesting a common cell of origin with disease evolution overlapping with related anterior mediastinal lymphomas.
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PMID:Mutational Landscape of Grey Zone Lymphoma. 3296 52