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.

一部分B细胞急性淋巴细胞白血病（B-ALL）患者将复发并屈服于治疗耐药性疾病。骨髓微环境可能支持B-ALL进展和逃避治疗。利用单细胞方法，我们证明了在常规化学疗法中疾病发作和随后的重新出现后，B-ALL骨髓免疫微环境的重塑。我们发现非经典单核细胞在B-ALL生存中的作用，并证明B-ALL诊断中的单核细胞丰度可预测儿科和成人B-ALL患者的生存。我们显示人类B-ALL blast改变血管化的微环境，促进单核细胞分化，而在B-ALL动物模型中消耗白血病相关的单核细胞则延长了体内疾病的缓解。我们对B-ALL免疫微环境的分析确定了B-ALL生存的外在调节因子，支持针对高风险B-ALL治疗的新的基于免疫的治疗方法。