Overall survival of patients with CLL treated with ibrutinib in the first line compared to second-line ibrutinib after chemotherapy/chemoimmunotherapy.

Objective: To evaluate the overall survival (OS) of patients with chronic lymphocytic leukemia (CLL) receiving either ibrutinib monotherapy as a first-line (1L) treatment or chemotherapy/chemoimmunotherapy-based (CT/CIT) regimens in 1L followed by ibrutinib in the second line (1L CT/CIT-2L ibrutinib) after disease progression by emulating a randomized trial comparing both treatment sequences.

Methods: Patient-level data from the RESONATE-2 trial (NCT01722487) and real-world PHEDRA databases were analyzed. Three scenarios were considered using the following data sources: (1) RESONATE-2, (2) combined RESONATE-2/PHEDRA, (3) combined RESONATE-2/PHEDRA for 1L ibrutinib and PHEDRA for 1L CT/CIT-2L ibrutinib.

PDLIM2 regulates transcription factor activity in epithelial-to-mesenchymal transition via the COP9 signalosome.

Epithelial cell differentiation and polarized migration associated with epithelial-to-mesenchymal transition (EMT) in cancer requires integration of gene expression with cytoskeletal dynamics. Here we show that the PDZ-LIM domain protein PDLIM2 (Mystique/SLIM), a known cytoskeletal protein and promoter of nuclear nuclear factor κB (NFκB) and signal transducer and activator of transcription (STAT) degradation, regulates transcription factor activity and gene expression through the COP9 signalosome (CSN). Although repressed in certain cancers, PDLIM2 is highly expressed in invasive cancer cells.

Sequestration of PDLIM2 in the cytoplasm of monocytic/macrophage cells is associated with adhesion and increased nuclear activity of NF-kappaB.

PDLIM2 (Mystique/SLIM) is a postsynaptic density-95/discs large/zonula occludens-1-Lin-11, Isl-1, Mec-3 (PDZ-LIM) domain protein expressed in the nucleus of T lymphocytes, where it promotes degradation of the p65 subunit of NF-kappaB. It is also expressed at the cytoskeleton in epithelial cells, where it is essential for cell migration. It is not known whether PDLIM2 function at the nucleus and cytoskeleton is linked and whether PDLIM2 subcellular location is regulated in hematopoietic cells.

Mystique is a new insulin-like growth factor-I-regulated PDZ-LIM domain protein that promotes cell attachment and migration and suppresses Anchorage-independent growth.

By comparing differential gene expression in the insulin-like growth factor (IGF)-IR null cell fibroblast cell line (R- cells) with cells overexpressing the IGF-IR (R+ cells), we identified the Mystique gene expressed as alternatively spliced variants. The human homologue of Mystique is located on chromosome 8p21.2 and encodes a PDZ LIM domain protein (PDLIM2).