Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia

A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy. We uncover a role for non-classical monocytes in B-ALL survival, and demonstrate monocyte abundance at B-ALL diagnosis is predictive of pediatric and adult B-ALL patient survival. We show that human B-ALL blasts alter a vascularized microenvironment promoting monocytic differentiation, while depleting leukemia-associated monocytes in B-ALL animal models prolongs disease remission in vivo. Our profiling of the B-ALL immune microenvironment identifies extrinsic regulators of B-ALL survival supporting new immune-based therapeutic approaches for high-risk B-ALL treatment. [Display omitted] •Patient B-ALL bone marrow displays extensively remodeled myeloid compartment•Monocyte abundance is predictive of pediatric and adult B-ALL patient survival•Human B-ALL promotes emergence of CD16+ non-classical monocytes ex vivo•Anti-CSF1R therapy enhances targeted treatment of Ph+ B-ALL models in vivo Using single-cell analysis of B cell acute lymphoblastic leukemia (B-ALL) patient samples, Witkowski et al. show that the frequency of non-classical monocytes predicts patient survival. Depletion of these monocytes improves treatment responsiveness in animal models of high-risk B-ALL.