A new family with a germline<i>ANKRD26</i>mutation and predisposition to myeloid malignancies

Márquez, Rafael; Hantel, Andrew; Lorenz, Rachelle; Neistadt, Barbara; Wong, Jerry; Churpek, Jane E.; Mardini, Nameer Al; Shaukat, Ismael; Gurbuxani, Sandeep; Miller, Jonathan L.; Godley, Lucy A.

doi:10.3109/10428194.2014.903476

Cited by 31 publications

(16 citation statements)

References 7 publications

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“…[31][32][33] In 420 families with thrombocytopenia 2, point mutations and one deletion mutation have been identified within a 22 base-pair region of the ANKRD26 5' untranslated region (UTR) ( Figure 2). 31-34 One family has been described with a missense mutation (D158G) encoded within exon 2.…”

Section: Managementmentioning

confidence: 99%

Inherited Predisposition to Acute Myeloid Leukemia

Godley

2014

Seminars in Hematology

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Section: Managementmentioning

confidence: 99%

Inherited Predisposition to Acute Myeloid Leukemia

Godley

2014

Seminars in Hematology

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“…Familial clustering of myeloid malignancies with autosomal dominant (AD) inheritance has been recognized phenotypically for over 100 years (reviewed in [4]), with the first molecular basis discovered through the identification of germline RUNX1 mutations associated with familial platelet disorder with predisposition to myeloid malignancy in 1999 (FPD-MM, OMIM #601399) [5]. Since that time, and recently accelerated by the advent of next-generation sequencing, a growing number of genes have been associated with AD germline predisposition to myeloid malignancies, including mutations in GATA2 [6] as described by us and others [7], as well as ANKRD26 [8], ETV6 [9], CEBPA [10], RBBP6 [11], TERT, TERC [12], DDX41 [13] and most recently mutations in SAMD9 [14] and SAMD9L [15,16]. This growing recognition and molecular identification of the germline predisposition to a subset of myeloid malignancies has been formalized in the most recent revision to the World Health Organisation guidelines [1].…”

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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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“…Interestingly, ANKRD26 5Ј-UTR mutations have also been associated with a predisposition for myeloid malignancies in conjunction with familial thrombocytopenia. 38,39 The role of ANKRD26 in megakaryopoiesis remains unclear. However, it was proposed recently that THC2 might be caused by abnormal MAP kinase signaling, in which 5Ј-UTR mutations in ANKRD26 result in loss of RUNX1 and FLI1 protein binding, both transcription factors that were implicated previously in inherited platelet disorders.…”

Section: Recent Developmentsmentioning

confidence: 99%

Genetic basis of congenital platelet disorders

Hinckley

Paola

2014

Hematology

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Over the past 4 decades, a better understanding of the genetic origins of inherited platelet disorders has illuminated avenues of investigation in megakaryopoiesis and has identified targets of pharmacologic intervention. Many of these discoveries have been translated into clinical medicine. The success of inherited platelet disorder research is underpinned by broader advances in methodology through the biochemical and molecular revolution of the 20 th and 21 st centuries, respectively. Recently, modern genomics techniques have affected platelet and platelet disorders research, allowing for the discovery of several genes involved in platelet production and function and for a deeper understanding of the RNA and miRNA networks that govern platelet function. In this short review, we focus on recent developments in the genetic elucidation of several disorders of platelet number and in the molecular architecture that determines the "genetic makeup" of a platelet in health and disease. Learning Objective• To provide readers with recent research discoveries of the genetic causes of platelet disorders

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A new family with a germlineANKRD26mutation and predisposition to myeloid malignancies

Cited by 31 publications

References 7 publications

Inherited Predisposition to Acute Myeloid Leukemia

Inherited Predisposition to Acute Myeloid Leukemia

Myeloid neoplasms with germline DDX41 mutation

Genetic basis of congenital platelet disorders

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