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

Matthew T. Witkowski, Igor Dolgalev, Nikki A. Evensen, Chao Ma, Tiffany Chambers, Kathryn G. Roberts, Sheetal Sreeram, Yuling Dai, Anastasia N. Tikhonova, Audrey Lasry, Chunxu Qu, Deqing Pei, Cheng Cheng, Gabriel A. Robbins, Joanna Pierro, Shanmugapriya Selvaraj, Valeria Mezzano, Marla Daves, Philip J. Lupo, Michael E. ScheurerCynthia A. Loomis, Charles G. Mullighan, Weiqiang Chen, Karen R. Rabin, Aristotelis Tsirigos, William L. Carroll, Iannis Aifantis

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)867-882.e12
JournalCancer Cell
Issue number6
StatePublished - Jun 8 2020


  • acute lymphoblastic leukemia
  • chemotherapy
  • immune microenvironment
  • monocytes
  • relapse
  • single cell
  • Prognosis
  • Humans
  • Child, Preschool
  • Infant
  • Male
  • Case-Control Studies
  • Young Adult
  • Antineoplastic Agents/pharmacology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/immunology
  • Monocytes/immunology
  • Tumor Microenvironment/immunology
  • Bone Marrow Transplantation
  • Adult
  • Female
  • Retrospective Studies
  • Single-Cell Analysis
  • Child
  • Proteome/analysis
  • Mice, Inbred C57BL
  • Survival Rate
  • Neoplasm Recurrence, Local/immunology
  • Animals
  • RNA-Seq
  • Adolescent

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Cell Biology


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