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ANKRD26-Related Thrombocytopenia and Predisposition to Myeloid Neoplasms

  • Germline Predisposition to Myeloid Neoplasms (M. Patnaik, Section Editor)
  • Published:
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Abstract

Purpose of review

This review describes ANKRD26-related thrombocytopenia (RT) from a molecular, clinical, and laboratory perspective, with a focus on the clinical decision-making that takes place in the diagnosis and management of families with ANKRD26-RT.

Recent findings

ANKRD26-related thrombocytopenia (ANKRD26-RT) is a non-syndromic autosomal dominant thrombocytopenia with predisposition to hematologic neoplasm. The clinical presentation is variable with moderate thrombocytopenia with normal platelet size and absent to mild bleeding being the hallmark which makes it difficult to distinguish from other inherited thrombocytopenias. The pathophysiology involves overexpression of ANKRD26 through loss of inhibitory control by transcription factors RUNX1 and FLI1. The great majority of disease-causing variants are in the 5′ untranslated region. Acute myeloid leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia have been reported to occur in the context of germline variants in ANKRD26, with the development of somatic driver mutations in hematopoietic regulators playing an important role in malignant transformation. In the absence of clear risk estimates of development of malignancy, optimal surveillance strategies and interventions to reduce risk of evolution to a myeloid disorder, multidisciplinary evaluation, with a strong genetic counseling framework is essential in the approach to these patients and their families.

Summary

Gene-specific expertise and a multidisciplinary approach are important in the diagnosis and treatment of patients and families with ANKRD26-RT. These strategies help overcome the challenges faced by clinicians in the evaluation of individuals with a rare, non-syndromic, inherited disorder with predisposition to hematologic malignancy for which large data to guide decision-making is not available.

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Authors and Affiliations

  1. Diagnostic Laboratories, Versiti, 638 N 18th St, Milwaukee, WI, 53233, USA

    Mia J. Sullivan, Elizabeth L. Palmer & Juliana Perez Botero

  2. Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    Juliana Perez Botero

Authors
  1. Mia J. Sullivan
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  2. Elizabeth L. Palmer
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  3. Juliana Perez Botero
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Correspondence to Juliana Perez Botero.

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This article is part of the Topical Collection on Germline Predisposition to Myeloid Neoplasms

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Sullivan, M.J., Palmer, E.L. & Botero, J.P. ANKRD26-Related Thrombocytopenia and Predisposition to Myeloid Neoplasms. Curr Hematol Malig Rep 17, 105–112 (2022). https://doi.org/10.1007/s11899-022-00666-4

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  • DOI: https://doi.org/10.1007/s11899-022-00666-4

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