Inflammatory pathways and the bone marrow microenvironment in inherited bone marrow failure syndromes.

Abstract

Inherited bone marrow failure syndromes (IBMFS) are a diverse group of genetic disorders characterized by insufficient hematopoietic cell production due to blood stem cell dysfunction. The most common syndromes are Fanconi Anemia, Diamond-Blackfan Anemia, and Shwachman-Diamond Syndrome. These conditions share a theme of chronically producing pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, TGF-β, IFN-I, and IFN-γ. Each of these cytokines can impact the bone marrow microenvironment and drive the pathophysiology of IBMFS. This review aims to provide the latest progress in the field regarding the mechanistic underpinnings of inflammation in these IBMFS, as well as the effect of inflammation on the bone marrow microenvironment. A comprehensive understanding of the inflammation in IBMFS will open new avenues for intervention to restore bone marrow stability and improve patient prognosis. Future research must include targeting these mechanisms to develop novel therapies that can potentially mitigate the effects of chronic inflammation in IBMFS.