Leukaemic transformation in a 10‐year‐old girl with <scp><i>SRP54</i></scp> congenital neutropenia

Calvo, Charlotte; Lainey, Élodie; Caye, Aurélie; Cuccuini, Wendy; Fenneteau, Odile; Yakouben, Karima; Bellanné‐Chantelot, Christine; Baruchel, André; Dalle, Jean‐Hugues; Leblanc, Thierry

doi:10.1111/bjh.18334

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…She received a cord blood transplant and has remained in remission for seven months. 12,35 While predisposition to leukemia has been established in patients with SDS, there is less evidence for predisposition to non-hematologic cancers. Seven cases with solid yrs: years; AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; IUGR: intrauterine growth restriction; CNS: central nervous system; NA: not available or applicable.…”

Section: Clinical Featuresmentioning

confidence: 99%

Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants

et al. 2023

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Shwachman-Diamond syndrome is a rare inherited bone marrow failure syndrome characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal abnormalities. In 10-30%, transformation to a myeloid neoplasm occurs. Approximately 90% of patients have biallelic pathogenic variants in the SBDS gene located on human chromosome 7q11. In the past several years, pathogenic variants in three other genes have been identified to cause similar phenotypes. These are DNAJC21, EFL1, and SRP54. Clinical manifestations involve multiple organ systems and those classically associated with the Shwachman-Diamond syndrome (bone, blood, and pancreas). Neurocognitive, dermatologic, and retinal changes may also be found. There are specific gene-phenotype differences. To date, SBDS, DNAJC21, and SRP54 variants have been associated with myeloid neoplasia. Common to SBDS, EFL1, DNAJC21, and SRP54 is their involvement in ribosome biogenesis or early protein synthesis. These four genes constitute a common biochemical pathway conserved from yeast to humans that involve early stages of protein synthesis and demonstrate the importance of this synthetic pathway in myelopoiesis. We propose to use the terms Shwachman-Diamond-like syndrome or Shwachman-Diamond syndromes.

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Section: Clinical Featuresmentioning

confidence: 99%

Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants

et al. 2023

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“…Most patients remained alive post‐HSCT. One patient died due to transplant‐related complications (Calvo et al, 2022; Sabulski et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…The current literature lacks standard guidelines and expert consensus recommendations for managing SRP54 pathogenic variants. Two reports published in 2022 described the first known malignant transformations in patients with SRP54 ‐related SCN, one with B‐cell acute lymphoblastic leukemia (Calvo et al, 2022) and the other with AML (Sabulski et al, 2022). Interestingly, both patients also harbored RUNX1 and CSF3R cytogenetic abnormalities, possibly associated with leukemogenesis in SCN (Skokowa et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…This leads to protein secretion defects that impair granulocyte differentiation, causing apoptosis and autophagy (Juaire et al, 2021). To date, there are two reports of malignant transformation in individuals with SRP54 pathogenic variants (Calvo et al, 2022; Sabulski et al, 2022). Here, we present a patient with SRP54 pathogenic variant and SCN, along with a literature review, and propose surveillance recommendations for MDS/AML and other associated complications.…”

Section: Introductionmentioning

confidence: 99%

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Severe congenital neutropenia, SRP54 pathogenicity, and a framework for surveillance

Fan

Vagher

Meznarich

et al. 2023

American J of Med Genetics Pt A

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Severe congenital neutropenia (SCN) is a rare disorder, often due to pathogenic variants in genes such as ELANE, HAX1, and SBDS. SRP54 pathogenic variants are associated with SCN and Shwachman‐Diamond‐like syndrome. Thirty‐eight patients with SRP54‐related SCN are reported in the literature. We present an infant with SCN, without classic Shwachman‐Diamond syndrome features, who presented with recurrent bacterial infections and an SRP54 (c.349_351del) pathogenic variant. Despite ongoing granulocyte colony‐stimulating factor therapy, this patient has no evidence of malignant transformation. Here we establish a framework for the future development of universal guidelines to care for this patient population.

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Discerning clinicopathological features of congenital neutropenia syndromes: an approach to diagnostically challenging differential diagnoses

Parisi,

Bledsoe

2024

J Clin Pathol

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The congenital neutropenia syndromes are rare haematological conditions defined by impaired myeloid precursor differentiation or function. Patients are prone to severe infections with high mortality rates in early life. While some patients benefit from granulocyte colony-stimulating factor treatment, they may still face an increased risk of bone marrow failure, myelodysplastic syndrome and acute leukaemia. Accurate diagnosis is crucial for improved outcomes; however, diagnosis depends on familiarity with a heterogeneous group of rare disorders that remain incompletely characterised. The clinical and pathological overlap between reactive conditions, primary and congenital neutropenias, bone marrow failure, and myelodysplastic syndromes further clouds diagnostic clarity.We review the diagnostically useful clinicopathological and morphological features of reactive causes of neutropenia and the most common primary neutropenia disorders: constitutional/benign ethnic neutropenia, chronic idiopathic neutropenia, cyclic neutropenia, severe congenital neutropenia (due to mutations inELANE,GFI1,HAX1,G6PC3,VPS45,JAGN1,CSF3R,SRP54,CLPBandWAS), GATA2 deficiency, Warts, hypogammaglobulinaemia, infections and myelokathexis syndrome, Shwachman-Diamond Syndrome, the lysosomal storage disorders with neutropenia: Chediak-Higashi, Hermansky-Pudlak, and Griscelli syndromes, Cohen, and Barth syndromes. We also detail characteristic cytogenetic and molecular factors at diagnosis and in progression to myelodysplastic syndrome/leukaemia.

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Leukaemic transformation in a 10‐year‐old girl with SRP54 congenital neutropenia

Cited by 4 publications

References 12 publications

Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants

Shwachman-Diamond syndromes: clinical, genetic, and biochemical insights from the rare variants

Severe congenital neutropenia, SRP54 pathogenicity, and a framework for surveillance

Discerning clinicopathological features of congenital neutropenia syndromes: an approach to diagnostically challenging differential diagnoses

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