Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

EZH2 catalyzes trimethylation of histone H3 lysine 27 (H3K27). Point mutations of EZH2 at Tyr641 and Ala677 occur in subpopulations of non-Hodgkin's lymphoma, where they drive H3K27 hypertrimethylation. Here we report the discovery of EPZ005687, a potent inhibitor of EZH2 (K(i) of 24 nM). EPZ005687 has greater than 500-fold selectivity against 15 other protein methyltransferases and has 50-fold selectivity against the closely related enzyme EZH1. The compound reduces H3K27 methylation in various lymphoma cells; this translates into apoptotic cell killing in heterozygous Tyr641 or Ala677 mutant cells, with minimal effects on the proliferation of wild-type cells. These data suggest that genetic alteration of EZH2 (for example, mutations at Tyr641 or Ala677) results in a critical dependency on enzymatic activity for proliferation (that is, the equivalent of oncogene addiction), thus portending the clinical use of EZH2 inhibitors for cancers in which EZH2 is genetically altered.
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PMID:A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. 2315 2

Somatic mutations in non-Hodgkin's lymphoma frequently activate EZH2, a protein methyltransferase responsible for H3K27 trimethylation. In this issue of Chemistry and Biology, Bradley and coworkers describe a new set of EZH2 inhibitors amenable to probing the targetable role of H3K27 trimethylation in lymphoma.
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PMID:Chemical cryptology of cancer's histone code. 2545 80

Therapy-related mixed phenotype acute leukemia (MPAL) following non-Hodgkin's lymphoma (NHL) is extremely rare. We present here the case of an elderly man, diagnosed with diffuse large B-cell lymphoma (DLBCL) through a tonsil biopsy. After treatment with seven cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) like regimen, the patient developed to MPAL (B/myeloid) with del(7)(q22), t(6;9)(p23;q34), DEK/NUP214 fusion, as well as EZH2 and TET2 mutations. The patient was successively treated with chemotherapy and allogenetic hematopoietic stem cell transplantation. Until recently he is still alive more than 23 months without relapse.
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PMID:Secondary mixed phenotype acute leukemia following chemotherapy for diffuse large B-cell lymphoma: a case report and review of the literature. 3193 38