TET2基因變異於兒童急性骨髓性白血病之盛行率及預後相關

背景及目的：兒童急性骨髓性白血病（acute myeloid leukemia, AML）佔兒童白血病的10％。隨著診斷及治療技術的進步，近年來成績已大幅進步，根據台灣兒童癌症基金會報告，五年無事件存活率（event free survival，EFS）為32%~54%及五年總存活率（overall survival，OS）為36%~66%。然而仍舊有高達三成的病人會產生復發，治療成績尚有進步空間且致病機轉仍不完全清楚。TET2（tet oncogene family member）為造血機制調節及腫瘤抑制基因，近年來其突變好發於成人急性骨髓性白血病且與預後相關，唯於兒童急性骨髓性白血病仍少有報導。本研究欲探討兒童急性骨髓性白血病患者TET2基因變異情況，分析與臨床表現及與預後相關性。方法：本研究分析自1997年1月至2010年7月期間至台大醫院就醫56位急性骨髓性白血病病童，取其診斷時骨髓檢體，建立PCR檢測TET2基因流程並定序。於兒童癌症基金會收集臨床表現，以卡方檢定、t檢定、Kaplan-Meier存活分析法及迴歸分析探討TET2基因變異情況與臨床表現及預後相關性。結果：本研究共分析56位病人，男女數目為34/22 (60.7%/39.3%)。平均年齡為9.07 ± 5.4（0.01~17.54）歲，發病時的白血球數目平均為86±103（1-392）k/uL。其中42.9%病患復發（N=24），55.4%病患死亡（N=31）。其中44人（78.6%）有TET2單一核苷酸多形性，只有一個位點（A1865G）是位於高保留區。分析TET2基因多形性與臨床表現及預後，發現並無相關。使用生物資訊學分析未報告過的點突變，其中3個單一核苷酸多形性經3個生物資訊軟體同時判定為「可能具致病性」，分析與臨床表現及預後並無相關。結論：TET2基因突變於兒童骨髓性白血病的盛行率遠較成人低，且其基因多形性與臨床表現、無事件存活時間和整體存活時間皆無相關。

關鍵字

兒童急性骨髓性白血病； TET2基因；基因多形性；單一核苷酸多形性

並列摘要

Background and Purpose. Acute myeloid leukemia (AML) accounts for 10% of childhood leukemia. The tet oncogene family member 2 (TET2) gene mutations are found in adult AML and is associated to prognosis. However, the report in childhood AML is limited. Here, we assess the prevalence of TET2 polymorphism in childhood AML and to identify its association with prognosis. Method. We collected pediatric patients in national Taiwan university hospital from January 1997 to June 2010. DNA was isolated from bone marrow cells at diagnosis and sequence analysis was carried out for TET2 gene. Chi-square, t-test, Kaplan-Meier survival method and regression analysis are used for testing the association of TET2 polymorphisms with clinical presentation and prognosis. Result. Total of 56 pediatric AML patients were enrolled. The mean age is 9.07 ± 5.4 (0.01~17.54) years. There are 34 (60.7%) males. Twenty-four (42.9%) patients had relapse and the overall survival rate is 45%. The prevalence of TET2 polymorphism is 78.6% (44/56). There was no association between TET2 polymorphism to clinical presentation or prognosis. Conclusions. The prevalence of TET2 mutation in pediatric AML patients is far lower than in adults and is not associated with clinical presentation or prognosis.

並列關鍵字

Acute myeloid leukemia ； Pediatric ； TET2 ； Single nucleotide polymorphism

參考文獻

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TET2基因變異於兒童急性骨髓性白血病之盛行率及預後相關

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