The CLL Research Consortium (CRC) is a multi-institutional research enterprise that catalyzes translational research on the genetic, biochemical, and immunologic basis of chronic lymphocytic leukemia (CLL). It maintains a sophisticated biorepository and a research management system that facilitate basic and clinical research studies on disease heterogeneity, response/resistance to therapy, and progression-free and overall survival among patients with CLL, or in any one CLL patient over time. To understand the biology of disease evolution, leukemia host-immune interactions, emergence of resistance to newly-developed targeted therapies and Richter Transformation (RT), and to develop improved treatments for patients with CLL, we have 4 highly interactive projects.

Project 1 (Croce PI) will examine the biologic/clinical significance of altered expression of a novel category of non-coding RNA. In addition, his team will identify  genes that are targeted by disease-dysregulated non-coding microRNA. These genes may encode proteins, such as ROR1, that are involved in pathogenesis and/or disease progression.

Project 2 (Wu PI) will characterize, by genome analyses, CLL cases with defined high- versus low-level expression of ROR1 to investigate how regulation of gene and pathway expression relate to clonal evolution and clinical outcome.

Project 3 (Kipps PI) will interrogate the signalosomes of developmentally-restricted non-canonical Wnt-receptors expressed on CLL cells. This project also will examine for activation of non-canonical Wnt signaling in CLL samples with high- vs low-level expression of ROR1 that will be studied in Projects 1, 2, and 4. This project will study the cross-talk between disparate Wnt-signaling pathways, and examine the expression-level and function of non-canonical Wnt receptors in CLL cells before, during, and after emergence of resistance to targeted therapies or Richters Transformation. This project also will investigate strategies that target non-canonical Wnt receptors for therapy.

Project 4 (Gribben PI) will examine the mechanisms of immune suppression in CLL and study whether ROR1 impacts on antigen-receptor interactions with the actin cytoskeleton, thereby potentially affecting the immune synapse and host immune function. It also will examine for progressive changes in the host immune system with disease progression.

The CRC has a strong, interactive infrastructure composed of four cores:

The Administrative (Admin) Core (Kipps) which provides scientific and administrative oversight and biomedical informatics support,

Core 1 (Neuberg) that assists in biostatistical design, implementation, and data analyses.

Core 2 (Rassenti) which is responsible for all tissue banking, sample trafficking, and sample-validation and characterization.

Core 3 (Wierda) facilitates clinical trials and provides clinical data to the Admin Core, which annotates these with samples collected in Core 2. This centralized, organized, and characterized sample distribution and interactions among the various projects lowers the threshold for research and discoveries for the CRC program and EXPEDITES the development of novel CLL therapies and enables the understanding the cause of RESISTANCE to specific therapies.

Administrative Core

Provides scientific and administrative oversight of CRC research, organizes meetings, facilitates communication, monitors for compliance with regulatory agencies, and provides biomedical informatics and data management for CRC projects and cores.

Core 2: Tissue Core

Provides for tissue banking, sample trafficking, sample validation, analyses of phenotypic, genotypic, and cytogenetic features of stored samples, processes CLL samples collected on clinical studies, and ensures access to tissue for correlative and hypothesis-testing research.

Core 3: Clinical Research Core

Facilitates development and execution of clinical trials, examines for new strategies that can achieve remission, facilitates correlative laboratory studies, and assessment of laboratory and clinical parameters.

External Advisory Committee

Reviews the progress of the CRC and related projects and assists in the selection of pilot projects.

ADVISORY MEMBER:

Steven Rosen
Provost, CSO, and Director of the Comprehensive Cancer Center at City of Hope

Peter Embi
President and CEO of the Regenstrief Institute

Charles Shiffer
Professor of Medicine and Oncology at Karmanos Cancer Institute

Jeanette Lee
Professor of Biostatistics at the University of Arkansas for Medical Sciences

Andrew Schorr
Founder of PatientPower.info; global patient-advocate, author of the “The Web-Savvy Patient”

Susan O’Brien
Professor and Associate Director at the Chao Family Comprehensive Cancer Center at UCI