Columbia University

Memorial Sloan Kettering Cancer Center

Universiteit Gent

Ghent University

Teresa Palomero

Adolfo A Ferrando

Raul Rabadan

Hans-Guido Wendel

Elisa Oricchio

Andrew L Wolfe

Konstantinos John Mavrakis

Kim De Keersmaecker

Franki Speleman

Pieter Van Vlierberghe

Peter Van Vlierberghe

The present invention relates to microRNAs (miRNAs) which are associated with cancer, particularly including hematologic malignancies, and particularly T-cell acute lymphoblastic leukemia (T-ALL), and to the assessment and modulation thereof in the treatment and management of cancer. The present invention is directed to methods and compositions for diagnosing and treating cancer, particularly T-ALL, by modulating miRNAs, and the use of miRNAs and antagonists thereof, particularly antagomirs, for predicting and assessing response to treatment, in assays for isolating and selecting antagonists, and as compositions for the treatment and management of cancer. Methods and compositions are provided for treatment or alleviation of cancer, particularly T-ALL, with antagonists/antagomirs of miRNAs, particularly one or more of miR-19b, miR-20a, miR26, miR92, miR148 and miR223.

Methods and compositions for the detection and treatment of cancer involving miRNAs and miRNA inhibitors and targets

Whole exome sequencing of 12 tumor-normal DNA pairs, RNAseq analysis and targeted deep sequencing identified new genetic alterations in PTCL transformation. These analyses identified highly recurrent epigenetic factor mutations in TET2, DN-MT3A and IDH2 as well as a new highly prevalent RHOA p.Gly17Val (NM_001664) mutation present in 22/35 (67%) of angioimmunoblastic T-cell lymphomas (AITL) and in 8/44 (18%) not otherwise specified PTCL (PTCL NOS) samples. Mechanistically, the RHOA Gly17Val protein interferes with RHOA signaling in biochemical and cellular assays, an effect potentially mediated by the sequestration of activated Guanine Exchange Factor (GEF) proteins. In addition, new and recurrent, genetic defects are described including mutations in FYN, ATM, B2M and CD58 implicating SRC signaling, impaired DNA damage response and escape from immune surveillance mechanisms in the pathogenesis of PTCL.

[object Object]

Growing community of inventors

New York, NY, United States of America

Teresa Palomero