Predicting the presence or absence of ringed sideroblasts in patients suspected of having a myelodysplastic syndrome and increased iron stores: a simple observation

Dorion, R. Patrick; Alomari, Mohammad; Wood, G. Craig

doi:10.1038/sj.leu.2402280

Cited by 1 publication

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“…Patients fulfilling criteria for RARS with elevated platelet counts are diagnosed as RARS-T. BM iron stores and diffuse pattern of iron deposits are often detected and have been correlated with the presence of RS. 2 During the years, abnormalities in mitochondrial iron have been implicated in the pathogenesis of both congenital and acquired SA. [3][4][5] Genetic studies found that heritable mutations in an erythroid-specific mitochondrial gene, delta aminolevulinate synthase (ALAS2) cause X-linked SA.…”

Section: Introductionmentioning

confidence: 99%

Distinct iron architecture in SF3B1-mutant myelodysplastic syndrome patients is linked to an SLC25A37 splice variant with a retained intron

et al. 2014

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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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