TY - JOUR
T1 - Role of the bone marrow immune microenvironment in chronic myelomonocytic leukemia pathogenesis
T2 - novel mechanisms and insights into clonal propagation
AU - Mangaonkar, Abhishek A.
AU - Patnaik, Mrinal M.
N1 - Funding Information:
MP is on the advisory board of Stemline Therapeutics and has received research funding from Kura Oncology. AM has received research funding from BMS.
Publisher Copyright:
© 2022 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - CMML
KW - dendritic cell biology
KW - immune microenvironment
KW - immunotherapy
KW - myeloid leukemias and dysplasias
KW - tumor microenvironment
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U2 - 10.1080/10428194.2022.2056175
DO - 10.1080/10428194.2022.2056175
M3 - Review article
C2 - 35377828
AN - SCOPUS:85129123323
SN - 1042-8194
VL - 63
SP - 1792
EP - 1800
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 8
ER -