Fig 4.

Involvement of C/EBPβ in non-infectious modes of hematopoiesis. (a) C/EBPβ is upregulated in the bone marrow of tumor-bearing hosts. C/EBPβ regulates the differentiation of myeloid-derived myeloid suppressor cells (MDSCs) and the expression of enzymes such as arginase and inducible nitric oxide synthase (iNOS), both of which are required for the lymphocyte-inhibitory activities of MDSCs. (b) In chronic phase chronic myeloid leukemia (CML), C/EBPβ is activated by signal transducer and activator of transcription 5 (STAT5), which is located downstream of BCR–ABL. C/EBPβ is involved in BCR–ABL-mediated myeloid expansion and leukemic stem cell exhaustion in chronic phase CML. (c) Acute promyelocytic leukemia (APL) is characterized by a promyelocytic leukemia-retinoic acid receptor α(PML-RARa)-mediated differentiation block at the promyelocyte stage. During the processes of differentiation-inducing therapy using all trans retinoic acid (ATRA), C/EBPβ is upregulated in the presence of PML-RARα and increases the number of neutrophils derived from APL cells by promoting their proliferation and differentiation.