Perturbation in iron homeostasis is a hallmark of some hematologic diseases. Abnormal sideroblasts with accumulation of iron in the mitochondria are named ring sideroblasts (RS). RS is a cardinal feature of refractory anemia with RS (RARS) and RARS with marked thrombocytosis (RARS/-T). Mutations in SF3B1, a member of the RNA splicing machinery are frequent in RARS/-T and defects of this gene were linked to RS formation. Here we showcase the differences in iron architecture of SF3B1-mutant and wild-type (WT) RARS/-T and provide new mechanistic insights by which SF3B1 mutations lead to differences in iron. We found higher iron levels in SF3B1 mutant vs WT RARS/-T by transmission electron microscopy/spectroscopy/flow cytometry. SF3B1 mutations led to increased iron without changing the valence as shown by the presence of Fe(2+) in mutant and WT. Reactive oxygen species and DNA damage were not increased in SF3B1-mutant patients. RNA-sequencing and Reverse transcriptase PCR showed higher expression of a specific isoform of SLC25A37 in SF3B1-mutant patients, a crucial importer of Fe(2+) into the mitochondria. Our studies suggest that SF3B1 mutations contribute to cellular iron overload in RARS/-T by deregulating SLC25A37.

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Case-hardening'' of the Ni-base superalloy IN718 has been achieved by low-temperature gas-phase carburization. After carburization under optimum conditions, the hardened surface layer (the ''case'') has about twice the hardness of the core (HV of %800) and contains %12 at pct carbon in interstitial solid solution. This causes a lattice parameter expansion of %1 pct perpendicular to the surface and, because of the mechanical constraint provided by the noncarburized core below, develops a large biaxial surface compressive residual stress (%1.9 GPa) parallel to the surface. Microstructural studies and X-ray diffractometry reveal no carbide precipitates in the case. In agreement with this observation, low-temperature carburization does not compromise the ductility and actually improves the crevice corrosion resistance of the alloy.