Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy

Owen, Carolyn; Toze, Cynthia L.; Koochin, Anna; Forrest, Donna L.; Smith, Clayton A.; Stevens, Jane; Jackson, Shannon; Poon, Man‐Chiu; Sinclair, Gary D.; Leber, Brian; Johnson, Peter; Macheta, Anthony; Yin, John; Barnett, Michael J.; Lister, T. A.; Fitzgibbon, Jude

doi:10.1182/blood-2008-05-156745

Cited by 227 publications

(206 citation statements)

References 22 publications

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“…After this report, a number of pedigrees have been reported and clinical evidences have been accumulated [18][19][20]. More than 30 pedigrees of FPD/AML have been reported to data.…”

Section: Familial Platelet Disorder (Fpd) With Propensity To Myeloid mentioning

confidence: 99%

“…After the acquisition of secondary genetic events, affected individuals of FPD/AML develop myeloid malignancies in many cases. However, some affected individuals also develop lymphoid neoplasms [20,[46][47][48].…”

Section: Additional Genetic Events For Mutant Clone Expansion and Leumentioning

confidence: 99%

“…When a patient is identified as an affected individual of FPD/AML and needs to undergo allogeneic stem cell transplantation, a sibling donor, who also has RUNX1 mutations, should not be chosen. Indeed, it has been reported that the use of donors who carry the same germ line mutations results in poor outcome [20,57]. In such a case, the use of HLA-matched unrelated donors should be considered [23].…”

Section: Clinical Management For Fpd/amlmentioning

confidence: 99%

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Myeloid neoplasms with germ line RUNX1 mutation

et al. 2017

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“…After this report, a number of pedigrees have been reported and clinical evidences have been accumulated [18][19][20]. More than 30 pedigrees of FPD/AML have been reported to data.…”

Section: Familial Platelet Disorder (Fpd) With Propensity To Myeloid mentioning

confidence: 99%

Section: Additional Genetic Events For Mutant Clone Expansion and Leumentioning

confidence: 99%

Section: Clinical Management For Fpd/amlmentioning

confidence: 99%

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Myeloid neoplasms with germ line RUNX1 mutation

et al. 2017

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“…This is a treatment issue problematic for all familial leukemia syndromes; for example we and others have documented multiple cases where this has occurred for germline RUNX1 mutated families (our unpublished data and [31,32]). Two recent studies in the literature document the outcomes of using germline DDX41 mutated donor cells for transplantation.…”

Section: Acquired Co-operating Mutations and Clonal Evolution In Germmentioning

confidence: 99%

Myeloid neoplasms with germline DDX41 mutation

et al. 2017

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to DDX41 mutation and highlights how each of these suggest potential therapeutic opportunities through the use of pathway-specific inhibitors.Keywords DDX41 · Myeloid malignancy · Myelodysplastic syndrome · Acute myeloid leukemia · Germline mutation · Predisposition Familial predisposition to myeloid neoplasmsMyeloid neoplasms are a heterogeneous group of diseases encompassing myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), all of which are characterized by abnormal growth and development of cells of the myeloid blood lineage. These disease groups can be further sub-categorized by a number of different morphological and molecular approaches which may correlate with responses to specific treatments [1]. AML and MDS Abstract Recently, DDX41 mutations have been identified both as germline and acquired somatic mutations in families with multiple cases of late-onset myelodysplastic syndrome (MDS) and/or acute myeloid leukemia. The majority of germline mutations are frameshift mutations suggesting loss of function with DDX41 acting as a tumor suppressor, and there is a common somatic missense mutation found in a majority of germline mutated tumors. Clinically, DDX41 mutations lead to development of high-risk MDS at an age similar to that observed in sporadic cohorts, presenting a unique challenge to hematologists in recognizing the familial context. Functionally, DDX41 has been shown to contribute to multiple pathways and processes including mRNA splicing, innate immunity and rRNA processing. Mutations in DDX41 result in aberrations to each of these in ways that could potentially impact on tumorigenesis-initiation, maintenance or progression. This review discusses the various molecular, clinical and biological aspects of myeloid malignancy predisposition due

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“…Familial occurrence of MDS and/ or AML is rare, tends to occur at younger presentation, and in families with more than one affected first-degree relative. It is associated with BM failure syndromes, in families with familial monosomy 7 [20], inherited telomere abnormalities [21], mutations of CEBPA [22,23], or in familial platelet disorder with propensity to develop myeloid malignancy (FPD/AML) in which germline RUNX1 mutations have been implicated [22,[24][25][26]. Moreover, although not yet associated with familial MDS/AML, mutations in TET2 and ASXL1 are common in MDS/MPN [27,28], and germline TET2 variants have been described in myeloid malignancy [29].…”

Section: Bm Fibrosis Has Long Been Associated With Mds [2-5]mentioning

confidence: 99%