Abstract
Bone marrow failure (BMF) syndromes are a heterogenous group of non-malignant hematologic diseases characterized by single- or multi-lineage cytopenia(s) with either inherited or acquired pathogenesis. Aberrant T or B cells or innate immune responses are variously involved in the pathophysiology of BMF, and hematological improvement after standard immunosuppressive or anti-complement therapies is the main indirect evidence of the central role of the immune system in BMF development. As part of this immune derangement, pro-inflammatory cytokines play an important role in shaping the immune responses and in sustaining inflammation during marrow failure. In this review, we summarize current knowledge of cytokine signatures in BMF syndromes.
Highlights
Bone marrow failure (BMF) syndromes are a heterogeneous group of non-malignant constitutional and acquired hematological diseases characterized by uni- or multi-lineage marrow and or peripheral blood cytopenia(s), regardless the presence of any other disorder that may affect marrow function [1,2,3,4]
hematopoietic stem cell (HSC) harboring a phosphatidyl-inositol glycan class A (PIG-A) mutation do not have any proliferative advantages compared with normal cells, as small paroxysmal nocturnal hemoglobinuria (PNH) clones can be found in healthy subjects; additional external events, such as BMF onset, should occur to induce disease development and progression [106,109]
BMF syndromes are characterized by hematopoietic failure and various grade of peripheral blood cytopenia(s); their pathogenesis varies even though a common immune signature could be identified [2,144]
Summary
Bone marrow failure (BMF) syndromes are a heterogeneous group of non-malignant constitutional and acquired hematological diseases characterized by uni- or multi-lineage marrow and or peripheral blood cytopenia(s), regardless the presence of any other disorder that may affect marrow function [1,2,3,4]. As polari zation and direct growth inhibition of HSCs, which leads to increased levels of growth factors for maintaining interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha, are involved in immune response norma hemopoiesis [8]. APC, antigen-presenting cells; MΦ, macrophage; CXCL, C-X-C motif chemokine; G-CSF, granulocyte polarization and direct growth inhibition of HSCs, which leads to increased levels of growth factors colony-stimulating factor; TPO, thrombopoietin; EPO, erythropoietin. Depletion of TNF-α producing macrophages in recipient mice abrogates BMF by blocking T cell migration into the BM and by reducing circulating levels of IFN-γ and TNF-α through induction of the master transcriptional regulator Tbx, which modulates gene expression in CD4+ and CD8+ T cells [33]. ILs, interleukins; IFNs, interferons; TNFs, tumor necrosis factors; CCL, CC chemokine ligands; CXCL, C-X-C motif chemokine; G-CSF, granulocyte colony-stimulating factor; TPO, thrombopoietin; EPO, erythropoietin; EGC, epidermal growth factor; VEGF, vascular endothelial growth factor; HGF, hepatocyte growth factor; GDF, growth differentiation factor; SELL, L-selectin; DKK1, Dickkopf-related protein 1; c-Mpl, thrombopoietin receptor
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