Oncostatin M deficiency: A newly recognized inherited bone marrow failure syndrome with potential predisposition to myeloid malignancy.

Inherited bone marrow failure syndromes (IBMFSs) are rare, genetically heterogeneous disorders characterized by BMF with possible increased risk of myeloid malignancies. Recent advances in genomic diagnostic techniques have identified a new IBMFS, including Oncostatin M (OSM) deficiency, which is an autosomal recessive condition linked to early-onset BMF with possible predisposition to myelodysplastic syndrome (MDS). OSM is a cytokine in the interleukin-6 family and regulates hematopoiesis through the OSM receptor and leukemia inhibitory factor receptor-mediated signaling, activating pathways essential for hematopoietic stem cell progenitor proliferation and differentiation. The reported cases from consanguineous families presented with early-onset cytopenias of variable severity, and some patients developed MDS. In patients with biallelic variants in OSM, hematologic improvement was observed following eltrombopag in two reported patients, while transfusion dependency and high-risk cytogenetics required hematopoietic stem cell transplantation. OSM deficiency is rare; its mechanistic and clinical parallels with other IBMFS underscore its importance. This review outlines the emerging evidence on OSM's function in hematopoiesis and its deficiency as a newly recognized IBMFS with a potential predisposition to MDS, highlighting the need for early genetic diagnosis and tailored treatment strategies.