Chronic Myelomonocytic Leukemia Microenvironment in Disease Progression and Therapy: Focus on Stepwise Reconfiguring of Myeloid-Immune Cell Interactions Driving Immune Tolerance.

PURPOSE OF THE REVIEW: To summarize evidence and provide an overview of the microenvironment and myeloid-immune cell interactions within the chronic myelomonocytic leukemia (CMML) microenvironment that drive mutation-agnostic pathways of disease progression.

RECENT FINDINGS: Recent work has demonstrated the importance of myeloid-immune cell interactions in CMML and related myeloid neoplasms. In particular, we focus on the bone marrow microenvironment of CMML, highlighting the role of clonal dendritic cell aggregates and their interaction with other myeloid cells such as monocytes and their precursors, and adaptive immune cells. Several drugs are currently under investigation that target the inflammasome, specific immune cell populations, and immune checkpoint inhibitors with limited success as monotherapy. Immune microenvironment plays a critical role in CMML disease biology and can be targeted for therapeutic benefit. Future research should focus on identifying pathways that are indispensable for progression.