Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aberrant DNA promoter methylation with associated gene silencing is a common epigenetic abnormality in acute lymphoblastic leukaemia (ALL) and is associated with poor survival. We have identified a family of transmembrane tyrosine phosphatase proteins as targets of hypermethylation in ALL and high-grade B cell lymphoma and demonstrated that this abnormal methylation correlates with transcript expression. PTPRG was methylated in 63% of ALL samples, PTPRK in 47%, PTPRM in 64% and PTPRO in 54% of cases, with most ALL samples containing methylation at multiple phosphatase loci. PTPRK promoter methylation was associated with a decreased overall survival in the cohort. Restoration of PTPRK transcript levels in leukaemia cells, where phosphatase transcript was silenced, reduced cell proliferation, inhibited colony formation and increased sensitivity to cytotoxic chemotherapy. These biological changes were associated with a reduction in levels of phosphorylated Erk1/2, Akt, STAT3 and STAT5 suggesting functional phosphatase activity after transcript re-expression. Methylation of the phosphatase promoters was reversible with decitabine and a histone deacetylase inhibitor, suggesting that PTPRK-mediated cell signalling pathways may be targeted with epigenetic therapies in lymphoid malignancy.
...
PMID:DNA methylation of membrane-bound tyrosine phosphatase genes in acute lymphoblastic leukaemia. 2404 99

Similar to most cancers, genome-wide DNA methylation profiles are commonly altered in pediatric acute lymphoblastic leukemia (ALL); however, recent observations highlight that a large portion of malignancy-associated DNA methylation alterations are not accompanied by related gene expression changes. By analyzing and integrating the methylome and transcriptome profiles of pediatric B-cell ALL cases and primary tissue controls, we report 325 genes hypermethylated and downregulated and 45 genes hypomethylated and upregulated in pediatric B-cell ALL, irrespective of subtype. Repressed cation channel subunits and cAMP signaling activators and transducers are overrepresented, potentially indicating a reduced cellular potential to receive and propagate apoptotic signals. Furthermore, we report specific DNA methylation alterations with concurrent gene expression changes within individual ALL subtypes. The ETV6-RUNX1 translocation was associated with downregulation of ASNS and upregulation of the EPO-receptor, while Hyperdiploid patients (> 50 chr) displayed upregulation of B-cell lymphoma (BCL) members and repression of PTPRG and FHIT. In combination, these data indicate genetically distinct B-cell ALL subtypes contain cooperative epimutations and genome-wide epigenetic deregulation is common across all B-cell ALL subtypes.
...
PMID:Epigenetic deregulation in pediatric acute lymphoblastic leukemia. 2439 48