Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman–Diamond syndrome cells

Cipolli, Marco; Boni, Christian; Penzo, Marianna; Villa, Isabella; Bolamperti, Simona; Baldisseri, Elena; Frattini, Annalisa; Porta, Giovanni; Api, Martina; Selicato, Nora; Roccia, Pamela; Pollutri, Daniela; Marinelli Busilacchi, Elena; Poloni, Antonella; Caporelli, Nicole; D'Amico, Giovanna; Pegoraro, Anna; Cesaro, Simone; Oyarbide, Usua; Vella, Antonio; Lippi, Giuseppe; Corey, Seth J.; Valli, Roberto; Polini, Alessandro; Bezzerri, Valentino

doi:10.1111/bjh.19134

Cited by 3 publications

(1 citation statement)

References 40 publications

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“…In conclusion, the extended growth charts reported in this study can potentially provide an excellent tool for clinicians dealing with SDS, facilitating more accurate followups of young patients with SDS. Additionally, these growth charts may assist investigators developing innovative therapies aimed at restoring the basic SDS defect [5,29,30], which are currently eliciting growing interest in the SDS scientific community.…”

Section: Discussionmentioning

confidence: 99%

Growth Charts for Shwachman–Diamond Syndrome at Ages 0 to 18 Years

Pegoraro,

Bezzerri,

Tridello

et al. 2024

Cancers

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Shwachman–Diamond syndrome (SDS) is one of the most common inherited bone marrow failure syndromes. SDS is characterized by hypocellular bone marrow, with a severe impairment of the myeloid lineage, resulting in neutropenia, thrombocytopenia, and, more rarely, anemia. Almost 15% of patients with SDS develop myelodysplastic syndrome or acute myeloid leukemia as early as childhood or young adulthood. Exocrine pancreatic insufficiency is another common feature of SDS. Almost all patients with SDS show failure to thrive, which is associated with skeletal abnormalities due to defective ossification. Considering these observations, it remains unfeasible to use the common growth charts already available for the general population. To address this issue, we report how we drew up growth charts of patients with SDS aged 0 to 18 years. We analyzed height, weight, and body max index (BMI) in 121 Italian patients with SDS. Results indicated that the 50th and 3rd percentiles of weight and height of the pediatric general population correspond to the 97th and 50th percentiles of patients with SDS aged 0–18 years, respectively. In addition, the percentage increment in weight of subjects aged 14–18 years was higher in patients with SDS than in the general population. SDS-specific growth charts, such as those described here, afford a new tool, which is potentially useful for both clinical and research purposes in SDS.

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Section: Discussionmentioning

confidence: 99%

Growth Charts for Shwachman–Diamond Syndrome at Ages 0 to 18 Years

Pegoraro,

Bezzerri,

Tridello

et al. 2024

Cancers

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From Challenge to Opportunity: How Shwachman–Diamond Syndrome Became a Promising Target for Therapy Development

Hars,

McReynolds

2024

Clin Pharma and Therapeutics

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Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman–Diamond syndrome

Lagos‐Monzon,

Ng,

Luca

et al. 2024

European J of Haematology

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Shwachman–Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (SBDS and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human‐derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of SBDS in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation‐related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., CHCHD2) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs.

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Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman–Diamond syndrome cells

Cited by 3 publications

References 40 publications

Growth Charts for Shwachman–Diamond Syndrome at Ages 0 to 18 Years

Growth Charts for Shwachman–Diamond Syndrome at Ages 0 to 18 Years

From Challenge to Opportunity: How Shwachman–Diamond Syndrome Became a Promising Target for Therapy Development

Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman–Diamond syndrome

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