The Role of Inflammation in CMML Pathobiology and Progression

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy characterized by monocytosis and dysplasia. While mutations in genes like TET2 and SRSF2 have helped us understand its molecular foundations, the role of inflammation in driving disease behavior is becoming increasingly evident. This review explores the role of inflammation in the biology and clinical progression of CMML, with a focus on its impact on disease initiation, progression, and potential therapeutic strategies.

Recent studies have shown that inflammatory cytokines, especially IL-6, TNF-α, and IL-8, are not just bystanders but active participants in promoting clonal hematopoiesis, immune dysregulation, and bone marrow dysfunction in CMML. Patients with systemic inflammation or autoimmune conditions are at a higher risk of developing CMML, suggesting a potential causal relationship. On the therapeutic front, drugs targeting cytokine pathways, such as ruxolitinib (a JAK inhibitor) and lenzilumab (an anti–GM–CSF antibody), have shown early promise in modifying disease activity and improving symptoms.

Inflammation plays a central role in CMML, from disease onset to transformation into acute leukemia. Understanding and targeting these inflammatory circuits may not only help slow disease progression but also improve quality of life for patients. As our knowledge grows, incorporating inflammation into both our diagnostic frameworks and treatment approaches will likely become standard in the care of CMML.