CLL cells may arise from B lymphocytes with differing immunoglobulin heavy chain variable region (IGHV) gene mutation status; those with unmutated IGHV tend to have a more aggressive clinical course compared to mutated IGHV counterparts. The disease biology is shaped by complex interactions between malignant B cells and the surrounding microenvironment—stromal and immune cells provide survival signals, drive proliferation, and support therapy resistance. Genomic alterations such as TP53 mutations and complex cytogenetic changes further contribute to treatment resistance
and disease progression.
Therapeutic strategies have evolved from traditional chemoimmunotherapy to the use of targeted agents, including inhibitors of Bruton’s tyrosine kinase (BTK) and B-cell leukemia/lymphoma-2 (BCL2). These drugs enable deeper and more durable remissions, especially for patients with high-risk molecular features. Nevertheless, CLL remains incurable for most, due to persistent drug resistance and disease evolution, particularly in aggressive variants such as accelerated CLL or Richter’s transformation, highlighting the continued need for innovative treatments and improved clinical trial designs.
The International Workshop on Chronic Lymphocytic Leukemia (iwCLL) is a leading global non-profit organization committed to improving outcomes for CLL patients worldwide. iwCLL hosts biennial meetings that serve as prominent forums for sharing pioneering research, developing international clinical and translational collaborations, harmonizing diagnostic and therapeutic standards, and shaping future directions in CLL management. The organization actively promotes educational initiatives and strives to improve access to state-of-the-art treatments, particularly in under-resourced countries.
Through its diverse membership, specialized subcommittees, and executive leadership, iwCLL advances clinical trial design, supports the translation of laboratory discoveries into patient care, and recognizes the contributions of sponsors and meeting organizers in building a unified, forward-looking CLL community.