Identification of an asymptomatic Shwachman–Bodian–Diamond syndrome mutation in a patient with acute myeloid leukemia

Autor: Seishi Ogawa, Toshiyuki Kitano, Shojiro Inano, Kensuke Fujiwara, Junya Kanda, Mizuki Watanabe, Sho Shibata, Naoto Kawasaki, Sumie Tabata, Akiko Fukunaga, Akifumi Takaori-Kondo, Hiroo Ueno, Yasuhito Nannya, Yoko Takiuchi, Yoshio Okamoto
Rok vydání: 2021
Předmět:
Zdroj: International Journal of Hematology. 115:428-434
ISSN: 1865-3774
0925-5710
DOI: 10.1007/s12185-021-03251-2
Popis: Shwachman-Diamond syndrome (SDS) is an autosomal recessive inherited disorder characterized by bone marrow failure, exocrine pancreatic dysfunction, and skeletal abnormalities. SDS is typically caused by a pathogenic mutation in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. Patients with SDS have an increased risk of developing acute myeloid leukemia (AML) and myelodysplastic syndromes. We identified germline biallelic SBDS mutations (p.K62X and p.I167M) in a 50-year-old AML patient who had never experienced the typical symptoms of SDS. The K62X mutation is one of the most common pathogenic mutations, whereas the significance of the I167M mutation was unclear. Based on cellular experiments, we concluded that the I167M mutation contributed to the development of AML, and chemotherapy including topoisomerase inhibitors, which induce DNA double-strand breaks, may have been toxic to this patient. Our experience indicates that some asymptomatic Shwachman-Bodian-Diamond syndrome mutations contribute to the development of leukemia, and that careful treatment selection may be warranted for patients harboring these mutations.
Databáze: OpenAIRE
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