Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity.

Clonal Hematopoiesis and Evolution to Hematopoietic Malignancies.

Inflammation is an important component of the tumor microenvironment. IL-1 is an inflammatory cytokine which plays a key role in carcinogenesis and tumor progression. IL-1 is subject to regulation by components of the IL-1 and IL-1 receptor (ILR) families. Negative regulators include a decoy receptor (IL-1R2), receptor antagonists (IL-1Ra), IL-1R8, and anti-inflammatory IL-37. IL-1 acts at different levels in tumor initiation and progression, including driving chronic non-resolving inflammation, tumor angiogenesis, activation of the IL-17 pathway, induction of myeloid-derived suppressor cells (MDSC) and macrophage recruitment, invasion and metastasis. Based on initial clinical results, the translation potential of IL-1 targeting deserves extensive analysis.

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IL-1 and IL-1 regulatory pathways in cancer progression and therapy.

Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer

MDSC: Markers, development, states, and unaddressed complexity.

The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression.

miR-125b promotes MLL-AF9-driven murine acute myeloid leukemia involving a VEGFA-mediated non-cell-intrinsic mechanism.

Objective
Most acute promyelocytic leukemia cases are characterized by the PML-RARa fusion oncogene and low white cell counts in peripheral blood.


Methods
Based on the frequent overexpression of miR-125-family miRNAs in acute promyelocytic leukemia, we examined the consequence of this phenomenon by using an inducible mouse model overexpressing human miR-125b.


Results
MiR-125b expression significantly accelerates PML-RARa-induced leukemogenesis, with the resultant induced leukemia being partially dependent on continued miR-125b overexpression. Interestingly, miR-125b expression led to low peripheral white cell counts to bone marrow blast percentage ratio, confirming the clinical observation in acute promyelocytic leukemia patients.


Conclusion
This study suggests that dysregulated miR-125b expression is actively involved in disease progression and pathophysiology of acute promyelocytic leukemia, indicating that targeting miR-125b may represent a new therapeutic option for acute promyelocytic leukemia.

Bo Guo

Papers

The DNA Methylcytosine Dioxygenase Tet2 Sustains Immunosuppressive Function of Tumor-Infiltrating Myeloid Cells to Promote Melanoma Progression.

miR-125b promotes MLL-AF9-driven murine acute myeloid leukemia involving a VEGFA-mediated non-cell-intrinsic mechanism.

MicroRNA-125b Accelerates and Promotes PML-RARa-driven Murine Acute Promyelocytic Leukemia.