ANKRD26遺伝子の5'UTRの変異と骨髄性悪性腫瘍の素因を持つ遺伝性血小板減少症との関係。エジプトでの研究

Relation between mutations in the 5' UTR of ANKRD26 gene and inherited thrombocytopenia with predisposition to myeloid malignancies. An Egyptian study.

• Nahla Ibrahim Zidan
• Doaa Metwally AbdElmonem
• Haitham Mohamed Elsheikh
• Elsayed Anany Metwally
• Wesam AbdElmonem Mokhtar
• Gamal Mohamed Osman

抄録

遺伝性血小板減少症は、血小板の数が減少し、出血傾向が非常に軽度なものから、特に手術時には生命を脅かすものまであることを特徴とする不均一な疾患群である。アンキリンリピートドメイン26（ANKRD26）の5'非翻訳領域（UTR）の変異が常染色体優勢型の血小板減少症の原因となっており，ANKRD26関連血小板減少症（ANKRD26 RT）として知られている．我々は，遺伝性血小板減少症を有する血縁関係のない患者 90 例を対象とした．さらに，ITP を有する 45 例の患者を調査した．末梢血および骨髄サンプルを採取して検査し、全患者についてANKRD26遺伝子の5°UTRにおける変異の分子検出を行った。また、罹患した対象者の拡大シリーズにおいて、変異と骨髄性悪性腫瘍の発生のスクリーニングを行った。ANKRD26遺伝子の変異は、遺伝性血小板減少症患者の10％で確認された。最も一般的な型はc.128G>Aとc.127A>Tであったが、ITP群では変異は認められなかった。血小板数の中央値は69 x10/L（43-106）であり，ほとんどの患者でMPVは正常であった（9.4-11.6）．また、突然変異群の延長シリーズでは、ITP群の延長シリーズと比較して、予想外に高い骨髄性悪性腫瘍の頻度が統計学的に有意に増加していた（<.001）。このことから、ANKRD26 RTは骨髄性悪性腫瘍の発症リスクの増加と関連しており、ANKRD26変異は治療上の意思決定を行うための貴重なツールとなり得ると結論づけられる。

Inherited thrombocytopenias are a heterogeneous group of diseases characterized by a reduced number of platelets and a bleeding tendency that ranges from very mild to life threatening especially in surgery. Mutations in the 5' untranslated region (UTR) of Ankirin repeat domain 26 (ANKRD26) are responsible for autosomal-dominant form of thrombocytopenia, that is known as ANKRD26-related thrombocytopenia (ANKRD26 RT), characterized by a moderate thrombocytopenia with mild propensity to bleeding and predisposition to hematological malignancies including AML and MDS. We included 90 unrelated patients with inherited thrombocytopenia. In addition, we investigated 45 patients with ITP. Peripheral blood and bone marrow samples were collected and examined and molecular detection of mutations in the 5︡ UTR of ANKRD26 gene was performed for all the patients. Also, screening of the mutation and development of myeloid malignancies in the extended series of the affected subjects was done. ANKRD26 mutations were identified in 10% of the patients with inherited thrombocytopenia. The most common types were c.128 G > A and c.127A>T, while no mutations were found in the ITP group. In those affected, the median number of platelets was 69 x10/L (43-106) with normal MPV in most of the patients (9.4-11.6). There was a statistically significant increase in the unexpected high frequency of myeloid malignancies in the extended series of the mutated subjects compared with the ITP group-extended series ( < .001). So, we can conclude that ANKRD26 RT is associated with increased risk for developing myeloid malignancies and ANKRD26 mutations can represent a valuable tool for making therapeutic decisions.