CLL Global Research Foundation will accept LOI submissions from June 1–21, 2026.

Research Priorities

Immune Dysfunction, Restoration, and Immune Effector Therapies
Aim: To define the mechanisms driving immune dysfunction in CLL and develop strategies to restore effective anti-tumor immunity.
This includes identifying defects in T-cell and NK-cell function, understanding tumor microenvironment–mediated immune suppression, and developing approaches to reverse immune exhaustion. Proposals should also advance immune-based therapies (e.g., CAR-T cells, bispecific antibodies) with a focus on improving efficacy, durability, and safety, and overcoming resistance.

Origin and Early Evolution of CLL
Aim: To elucidate the biological origins of CLL and the factors driving progression from monoclonal B-cell lymphocytosis (MBL) to clinically significant disease.
This includes identifying key genomic, epigenetic, and microenvironmental changes involved in disease initiation and early clonal evolution. Proposals should seek to define mechanisms of progression, improve risk stratification, and inform strategies for early detection and prevention.

Novel Therapeutic Targets and Approaches
Aim: To identify and validate new molecular targets and develop innovative therapeutic strategies for CLL.
Proposals should focus on uncovering key biological drivers of disease and resistance, particularly in the setting of inhibitor-refractory CLL. Areas of interest include the discovery of novel targets, development of next-generation agents, and rational combination strategies designed to overcome resistance and improve depth and durability of response. Approaches that integrate translational insights with clinical application are strongly encouraged.

High-Risk, Genomically Complex CLL and Richter Transformation
Aim: To advance the understanding and treatment of aggressive and high-risk forms of CLL, including Richter transformation.
Proposals should investigate the biological mechanisms underlying Richter transformation and high-risk disease, including TP53 disruption and genomic complexity. Areas of interest include improving early detection and diagnosis, identifying drivers of early relapse and treatment resistance, and developing effective therapeutic strategies to improve outcomes. Studies focused on novel treatments, including targeted and immune-based approaches, are encouraged, particularly those addressing poor durability of current therapies.