Role of the bone marrow immune microenvironment in chronic myelomonocytic leukemia pathogenesis: novel mechanisms and insights into clonal propagation

Abhishek A. Mangaonkar, Mrinal M. Patnaik

Research output: Contribution to journalReview articlepeer-review

Abstract

Recent studies in chronic myelomonocytic leukemia (CMML) involving clonal dendritic cell (DC) aggregates and association with systemic immune dysregulation have highlighted novel and potentially targetable pathways of disease progression. CMML DC aggregates are populated by heterogeneous cell types such as CD123+ plasmacytoid dendritic cells (pDCs), CD11c + myeloid-derived DCs (mDCs), myeloid-derived suppressor cells (MDSCs), monocytes, and associate with an immune checkpoint called indoleamine 2,3-dioxygenase (IDO). Systemically, these IDO + DC aggregates are associated with immune tolerance marked by regulatory T cell expansion, likely mediated by aberrant DC-T cell interactions occurring within the bone marrow (BM) microenvironment. Somatic mutational events in CMML such as ASXL1 and NRAS mutations cooperate to induce T cell exhaustion and contribute toward disease progression to acute myeloid leukemia (AML). In this review, we explore the role of aging-induced alterations in the BM immune microenvironment, aberrant innate immune and proinflammatory signaling, and the adaptive immune system in CMML.

Original languageEnglish (US)
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - 2022

Keywords

  • CMML
  • dendritic cell biology
  • immune microenvironment
  • immunotherapy
  • myeloid leukemias and dysplasias
  • tumor microenvironment

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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