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Germline Mutations Associated with Leukemia in Childhood: New Discoveries and Emerging Phenotypes

  • Genetic Counseling and Clinical Testing (BS LeRoy and N Callanan, Section Editors)
  • Published:
Current Genetic Medicine Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Acute leukemia is the most common cancer of childhood. The pathogenesis of childhood leukemia is multifactorial, and most cases occur sporadically. Although the majority of genetic changes are acquired somatic mutations, recent discoveries have revealed that inherited germline mutations are present in an increasing proportion of children, predisposing them to leukemia.

Recent Findings

Recently described germline mutations in ETV6, SH2B3, and PAX5 have been associated with increased risks of acute lymphoblastic leukemia (ALL). A high incidence of germline mutations in GATA2 is seen in pediatric myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). Susceptibility genes for adult leukemia are found at increased incidence in children with MDS/AML. Recent findings have broadened the phenotype of inherited bone marrow failure syndromes, with a decreased emphasis on phenotypic abnormalities.

Summary

Newly identified germline susceptibilities to hematologic malignancies are emerging at a rapid pace with the advent of next-generation sequencing approaches. A higher incidence of germline mutations accounts for childhood leukemia more than previously thought, and affected children do not necessarily fit into previously described syndromic presentations; therefore, careful clinical consideration is required for accurate diagnosis. Furthermore, children with inherited predisposition require a multidisciplinary approach to ensure proper evaluation and treatment, including but not limited to genetic counseling for the patient and family members and close management by a hematologist and oncologist, plus evaluations by a psychologist, as well as by a stem cell transplantation specialist.

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Authors and Affiliations

  1. Department of Clinical Cancer Genetics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0428, Houston, TX, 77030, USA

    Sarah A. Bannon

  2. Department of Pediatrics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0428, Houston, TX, 77030, USA

    Jessica Foglesong

  3. Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0428, Houston, TX, 77030, USA

    Courtney D. DiNardo

Authors
  1. Sarah A. Bannon
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  2. Jessica Foglesong
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  3. Courtney D. DiNardo
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Correspondence to Courtney D. DiNardo.

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All authors declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Genetic Counseling and Clinical Testing

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Bannon, S.A., Foglesong, J. & DiNardo, C.D. Germline Mutations Associated with Leukemia in Childhood: New Discoveries and Emerging Phenotypes. Curr Genet Med Rep 5, 59–65 (2017). https://doi.org/10.1007/s40142-017-0118-5

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  • DOI: https://doi.org/10.1007/s40142-017-0118-5

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