白血病の治療を受けた子供の遺伝的不安定性の出現

B A Finette¹, A C Homans, R J Albertini

¹Department of Pediatrics, Vermont Cancer Center, University of Vermont, Medical Alumni Building, Burlington, VT 05405, USA. finette@salus.med.uvm.edu

Science (New York, N.Y.)

|April 25, 2000

まとめ

白血病の化学療法は,健康なT細胞の遺伝的不安定性を引き起こし,突然変異を引き起こす可能性があります. この発見は,一部の患者で二次がんと薬剤耐性を発症させる可能性のあるメカニズムを示唆しています.

科学分野:

免疫学免疫学とは
腫瘍学腫瘍学
遺伝学遺伝学とは

背景:

癌細胞は,遺伝的不安定性が特徴です.
非悪性細胞に対する化学療法の効果は,十分に理解されていません.
B系統の急性リンパ球性白血病 (ALL) は,血液と骨髄の癌である.

研究の目的:

B系統ALLに対する化学療法後の非悪性T細胞で遺伝的不安定性が発生するかどうかを調査する.
T細胞における化学療法による遺伝的不安定性の潜在的影響を調査する.

主な方法:

B系統ALLを治療した患者からのT細胞の分析.
ヒポキサンチン・グアニン・フォスフォリボシルトランスフェラーゼ (HPRT) レポーター遺伝子における変異の検出.
T細胞受容体β (TCRbeta) 遺伝子再配列の特徴付け独立した細胞集団を識別する.

主要な成果:

治療を受けた患者のT細胞のHPRT遺伝子に複数の変異が発見されました.
変異T細胞は,同一のTCRbeta遺伝子ハイパー変異領域を示し,独立した起源を示した.
これらの発見は,非悪性T細胞における遺伝的不安定性フェノタイプと一致しています.

結論:

がん治療,特にALLの化学療法では,特定の個体における非悪性T細胞の遺伝的不安定性を誘発することがあります.
この不安定性は,第2の悪性腫瘍の発生に寄与するメカニズムである可能性があります.
化学療法によって引き起こされるT細胞の遺伝的不安定性も,薬剤耐性の獲得に役割を果たす可能性がある.

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