Marrow failure: a window into ribosome biology (original) (raw)

“…14,15 Identification of the cell types specifically affected by dysfunction of ribosomal genes will thus be critical in deciphering the underlying molecular mechanisms driving disease pathology, ultimately enabling targeted therapies. However, progress in understanding the pathophysiology of SDS is limited by the lack of a robust mammalian model faithfully recapitulating neutropenia.…”

Section: Introductionmentioning

“…14,15 Identification of the cell types specifically affected by dysfunction of ribosomal genes will thus be critical in deciphering the underlying molecular mechanisms driving disease pathology, ultimately enabling targeted therapies. However, progress in understanding the pathophysiology of SDS is limited by the lack of a robust mammalian model faithfully recapitulating neutropenia.…”

Section: Introductionmentioning

“…Several other IBMFSs are also caused by an abnormal translational machinery. These include Diamond-Blackfan anemia and the canonical SDS (29). While all these disorders (and others) are associated with mutations that affect 40S or 60S ribosomal subunits and/or their assembly (with the exception of 2 sporadic cases of aplastic anemia that were mutated in another SRP subunit [SRP72] [ref.…”

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“…For example, the developmental defects caused by RPS14 haploinsufficiency in 5q-syndrome and the loss of Rps19/Rpl11 in DiamondBlackfan anemia have been shown to depend on the activation of p53 [2]. Rpl22 and its paralog Rpl22l1 regulate the generation of hematopoietic stem cells (HSC) by antagonistically regulating the translation of Smad1, which is critical for induction of the transcription factor Runx1 that drives HSC emergence [3].…”

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