High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder

Preudhomme, Claude; Renneville, Aline; Bourdon, Violaine; Philippe, N; Roche‐Lestienne, Catherine; Boissel, Nicolas; Dhédin, Nathalie; André, Jean‐Marie; Cornillet‐Lefèbvre, Pascale; Baruchel, André; Mozziconacci, Marie‐Joëlle; Sobol, Hagay

doi:10.1182/blood-2008-07-168260

Cited by 161 publications

(146 citation statements)

References 23 publications

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“…Four pathogenic or likely pathogenic variants were identified that are previously known to cause IT. These were found in patients; 54 ( GATA1 ; c.1240T>C, p.*414Arg+41), 59 ( RUNX1 ; c.386C>A, p.Ala129Glu), 70 ( GFI1B ; c.503G>T, p.Cys168Phe), and 64 ( MYH9 ; c.2152C>T, p.Arg718Trp) 3 , 15 , 16 , 17 …”

Section: Resultsmentioning

confidence: 95%

A comprehensive targeted next‐generation sequencing panel for genetic diagnosis of patients with suspected inherited thrombocytopenia

Johnson

Doak

Allsup

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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BackgroundInherited thrombocytopenias (ITs) are a heterogeneous group of disorders characterized by low platelet counts and often disproportionate bleeding with over 30 genes currently implicated. Previously the UK‐GAPP study using whole exome sequencing (WES) identified a pathogenic variant in 19 of 47 (40%) patients of which 71% had variants in genes known to cause IT.AimsTo employ a targeted next‐generation sequencing platform to improve efficiency of diagnostic testing and reduce overall costs.MethodsWe have developed an IT‐specific gene panel as a pre‐screen for patients prior to WES using the Agilent SureSelectQXT transposon‐based enrichment system.ResultsThirty‐one patients were analyzed using the panel‐based sequencing, of which; 10% (3/31) were identified with a classified pathogenic variant, 16% (5/31) were identified with a likely pathogenic variant, 51% (16/31) were identified with variants of unknown significance, and 23% (7/31) were identified with either no variant or a benign variant.Discussion and ConclusionAlthough requiring further clarification of the impact of the genetic variations, the application of an IT‐specific next generation sequencing panel is an viable method of pre‐screening patients for variants in known IT‐causing genes prior to WES. With an added benefit of distinguishing IT from idiopathic thrombocytopenic purpura (ITP) and the potential to identify variants in genes known to have a predisposition to hematological malignancies, it could become a critical step in improving patient clinical management.

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Section: Resultsmentioning

confidence: 95%

A comprehensive targeted next‐generation sequencing panel for genetic diagnosis of patients with suspected inherited thrombocytopenia

Johnson

Doak

Allsup

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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“…Three variants, ANKRD26; c.-126T>G in F2.I, MYH9; c.3493C>T (rs80338829) in F9.I and RUNX1; c.530G>A in F19.I and F19.II have been previously associated with IT. 1,19,20 The remaining three variants that have been previously observed occurred at frequencies of <0.005 (0.05%) in available databases. One of the databases scrutinized was that of the ExAC consortium (http://exac.broadinstitute.org) which may include data from individuals with low platelet counts who were either undiagnosed or recruited through an unrelated study (Table 2).…”

Section: Variants In Known Thrombocytopenia-causing Genesmentioning

confidence: 99%

“…One variant, RUNX1; p.Arg177Gln, observed in F19.I and F19.II has been previously reported as a causative germline mutation of a familial platelet disorder in two individuals from the same pedigree. 20 The variations consisted of five missense variants, two splice-site variants and one nonsense variant. One splice-site variation, c.270+1G>T, was present within three affected individuals from two separate families (F13 and F14).…”

Section: Variants In Known Thrombocytopenia-causing Genesmentioning

confidence: 99%

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Johnson¹,

Lowe²,

Fütterer³

et al. 2016

Haematologica

119

135

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“…On the other hand, a high frequency of RUNX1 biallelic mutations in the patients with FPD/AML has been reported from a French group [42,43]. Besides RUNX1 biallelic mutations, a variety of mutations were identified at the AML stage, such as mutations in FLT3, KRAS, CBL, TP53, SRSF2, SF3B1, TET2, and DNMT3A [43].…”

Section: Additional Genetic Events For Mutant Clone Expansion and Leumentioning

confidence: 99%

Myeloid neoplasms with germ line RUNX1 mutation

et al. 2017

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High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder

Abstract: Familial platelet disorder (FPD),

Cited by 161 publications

References 23 publications

A comprehensive targeted next‐generation sequencing panel for genetic diagnosis of patients with suspected inherited thrombocytopenia

A comprehensive targeted next‐generation sequencing panel for genetic diagnosis of patients with suspected inherited thrombocytopenia

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

Myeloid neoplasms with germ line RUNX1 mutation

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