The isochromosome i(7)(q10) carrying c.258+2t&gt;c mutation of the SBDS gene does not promote development of myeloid malignancies in patients with Shwachman syndrome

Minelli, Antonella; Maserati, Emanuela; Nicolis, Elena; Zecca, Marco; Sainati, Laura; Longoni, Daniela; Curto, Francesco Lo; Menna, Giuseppe; Poli, Furio; Paoli, Elena De; Cipolli, Marco; Locatelli, Franco; Pasquali, Francesco; Danesino, Cesare

doi:10.1038/leu.2008.369

Cited by 57 publications

(51 citation statements)

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“…Two recurrent cytogenetic anomalies have been observed, i(7)(q10) and del(20q), which can be indolent and sometimes even transient. [25][26][27][28][29][30][31][32][33] However, these same abnormalities can also announce or be associated with a frank malignant outcome, [34][35][36] as we observed in two cases in this survey. In addition to the patients with i(7)(q10) and del(20q), we also observed an indolent profile in two other patients, one with t(16;20) in addition to i(7)(q10) and one with a complex abnormality of chromosome 9 (Online Supplementary Table S1).…”

Section: Discussionmentioning

confidence: 52%

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

et al. 2012

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The online version of this article has a Supplementary Appendix. BackgroundPatients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. Design and MethodsOne hundred and two patients with Shwachman-Diamond syndrome, with a median followup of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20×10 9 /L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant. ResultsSevere cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by nonmalignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%-38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. ConclusionsPatients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value.Key words: Shwachman-Diamond syndrome, genotype, aplastic anemia, secondary leukemia, cytopenia, myelodysplasia, monosomy 7.Citation: Donadieu J, Fenneteau O, Beaupain B, Beaufils S, Bellanger F, Mahlaoui N, Lambilliotte A, Aladjidi N, Bertrand Y, Mialou V, Perot C, Michel G, Fouyssac F, Paillard C, Gandemer V, Boutard P, Schmitz J, Morali A, Leblanc T, Bellanné-Chantelot C, and Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

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Section: Discussionmentioning

confidence: 52%

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

et al. 2012

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“…Mutations of the SBDS gene were analyzed as previously described. 17 The presence of two of the common mutations…”

Section: Design and Methodsmentioning

confidence: 99%

Ubiquitin-proteasome-rich cytoplasmic structures in neutrophils of patients with Shwachman-Diamond syndrome

Necchi¹,

Minelli²,

Sommi³

et al. 2012

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundShwachman-Diamond syndrome is an autosomal recessive disorder in which severe bone marrow dysfunction causes neutropenia and an increased risk of leukemia. Recently, novel particulate cytoplasmic structures, rich in ubiquitinated and proteasomal proteins, have been detected in epithelial cells and neutrophils from patients with Helicobacter pylori gastritis and several epithelial neoplasms. Design and MethodsBlood neutrophils from 13 cases of Shwachman-Diamond syndrome -ten with and three without SBDS gene mutation -and ten controls were investigated by confocal microscopy and ultrastructural immunocytochemistry using antibodies against ubiquitinated proteins, proteasomes, p62 protein, and Helicobacter pylori VacA, urease and outer membrane proteins. ResultsMany extensively disseminated particulate cytoplasmic structures, accounting for 22.78±5.57% (mean ± standard deviation) of the total cytoplasm, were found in blood neutrophils from mutated Shwachman-Diamond syndrome patients. The particulate cytoplasmic structures showed immunoreactivity for polyubiquitinated proteins and proteasomes, but no reactivity for Helicobacter pylori products, which are present in particulate cytoplasmic structures of Helicobacter pylori-positive gastritis. Neutrophils from patients with Shwachman-Diamond syndrome frequently showed p62-positive autophagic vacuoles and apoptotic changes in 5% of cells. No particulate cytoplasmic structures were observed in most control neutrophils; however, in a few cells from two cases we noted focal development of minute particulate cytoplasmic structures, accounting for 0.74±0.56% of the total cytoplasm (P<0.001 versus particulate cytoplasmic structures from mutated Shwachman-Diamond syndrome patients). Neutrophils from non-mutated Shwachman-Diamond-syndrome-like patients resembled controls in two cases, and a third case showed particulate cytoplasmic structure patterns intermediate between those in controls and those in mutated Shwachman-Diamond syndrome patients. ConclusionsParticulate cytoplasmic structures are a prominent feature of neutrophils from patients with Shwachman-Diamond syndrome. They may help us to understand the mechanism of granulocyte dysfunction and the neoplastic risk of the disease.Key words: ubiquitin, proteasome, particulate cytoplasmic structure, Shwachman-Diamond syndrome, autophagy, apoptosis.Citation: Necchi V, Minelli A, Sommi P, Vitali A, Caruso R, Longoni D, Frau MR, Nasi C, De Gregorio F, Zecca M, Ricci V, Danesino C, and Solcia E. Ubiquitin-proteasome-rich cytoplasmic structures in neutrophils of patients with Shwachman-Diamond syndrome. Haematologica 2012;97(7):1057-1063. doi:10.3324/haematol.2011 This is an open-access paper. Ubiquitin-proteasome-rich cytoplasmic structures in neutrophils of patients with Shwachman-Diamond syndrome ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

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“…On the other hand, some reports counter the risk of myeloid malignancies in SDS patients with i(7q), indicating a good prognosis of SDS with i(7q) 9, 10. However, refractory cytopenia in SDS patients with i(7q) was described in these articles 9, 10, and the significance of i(7q) in cytopenia has not yet been clarified.…”

Section: Discussionmentioning

confidence: 97%

“…The most common abnormality of bone marrow is isochromosome (7)(q10), (i(7q)), which accounts for up to 40% of abnormalities 2. The significance of i(7q) is controversial 7, 8, 9, 10. The present report describes two male siblings with SDS, one that harbored cytogenetic abnormality of i(7q) in bone marrow and required allogeneic HCT.…”

Section: Introductionmentioning

confidence: 83%

“…However, refractory cytopenia in SDS patients with i(7q) was described in these articles 9, 10, and the significance of i(7q) in cytopenia has not yet been clarified. The clinical courses of the siblings who harbored the same compound mutations although severe cytopenia was manifested in only the sibling with i(7q) indicated that i(7q) is associated with the progression of severe bone marrow failure in SDS patients.…”

Section: Discussionmentioning

confidence: 99%

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Association of isochromosome (7)(q10) in Shwachman–Diamond syndrome with the severity of cytopenia

Shimosato

Tanoshima

Tsujimoto

et al. 2017

Clinical Case Reports

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The isochromosome i(7)(q10) carrying c.258+2t>c mutation of the SBDS gene does not promote development of myeloid malignancies in patients with Shwachman syndrome

Cited by 57 publications

References 16 publications

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

Ubiquitin-proteasome-rich cytoplasmic structures in neutrophils of patients with Shwachman-Diamond syndrome

Association of isochromosome (7)(q10) in Shwachman–Diamond syndrome with the severity of cytopenia

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