Abstract: Methods are described herein for identifying and/or treating lymphoma patients that have one or more genomic mutations in a coding region of at least one BCL10 allele. Such patients can be resistant to commonly used cancer treatments and can benefit instead from treatment with at least one MALT1 inhibitor.

Abstract: The invention relates generally to methods for diagnosis and treatment of follicular lymphoma or diffuse large B cell lymphoma. Specifically, the invention relates to detecting a lysine (K)-specific methyltransferase 2D (KMT2D) alteration to diagnose or treat follicular lymphoma or diffuse large B cell lymphoma.

Abstract: The invention provides compositions and methods for blocking the BCL6 BTB domain with small molecule, non-peptide compounds as disclosed and claimed herein. BCL6 is a transcriptional repressor of the BTB-POZ (brie a brae, tramtrack, broad complex/pox virus zincfinger) family of proteins. It is required for normal development of germinal center (GC) B-cells and is also the most commonly involvedoncogene in diffuse large B-celllymphomas (DLBCLs), and constitutive expression of BCL6 in GC B-cells causes DLBCL in mice.

Abstract: MALT1 cleavage activity is linked to the pathogenesis of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL), a chemo-resistant form of DLBCL. We developed a MALT1 activity assay and identified chemically diverse MALT1 inhibitors. A selected lead compound MI-2 featured direct binding to MALT1 and suppression of its protease function. MI-2 concentrated within human ABC-DLBCL cells and irreversibly inhibited cleavage of MALT1 substrates. This was accompanied by suppression of NF-KB reporter activity, inhibition of nuclear localization of c-REL and downregulation of NF-KB target gene signature. Most notably, MI-2 was non-toxic to mice, and displayed potent and specific activity against ABC-DLBCL cell lines in vitro, and xenotransplanted ABC-DLBCL tumors in vivo. The compound was also effective against primary human non-GCB-DLBCLs ex vivo.

Abstract: The invention provides compositions and methods for blocking the BCL6 BTB domain with small molecule, non-peptide compounds as disclosed and claimed herein. BCL6 is a transcriptional repressor of the BTB-POZ (brie a brae, tramtrack, broad complex/pox virus zincfinger) family of proteins. It is required for normal development of germinal center (GC) B-cells and is also the most commonly involvedoncogene in diffuse large B-celllymphomas (DLBCLs), and constitutive expression of BCL6 in GC B-cells causes DLBCL in mice.

Abstract: MALT1 cleavage activity is linked to the pathogenesis of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL), a chemo-resistant form of DLBCL. We developed a MALT1 activity assay and identified chemically diverse MALT1 inhibitors. A selected lead compound MI-2 featured direct binding to MALT1 and suppression of its protease function. MI-2 concentrated within human ABC-DLBCL cells and irreversibly inhibited cleavage of MALT1 substrates. This was accompanied by suppression of NF-KB reporter activity, inhibition of nuclear localization of c-REL and downregulation of NF-KB target gene signature. Most notably, MI-2 was non-toxic to mice, and displayed potent and specific activity against ABC-DLBCL cell lines in vitro, and xenotransplanted ABC-DLBCL tumors in vivo. The compound was also effective against primary human non-GCB-DLBCLs ex vivo.

Abstract: The invention is directed to a compound that binds to a BCL6 lateral groove and prevents binding of a corepressor to the lateral groove. The present invention is further directed to methods for blocking corepressor binding to a BCL6 lateral groove, methods for inhibiting BCL6 repression in a mammalian cell, and methods for treating a mammal with cancer, wherein the cancer requires BCL6 repression. The present invention is further directed to polypeptides comprising a portion of the corepressor binding site for BCL6 and related polynucleotides and vectors.