Yokokawa Yuichi, Taki Tomohiko, Chinen Yoshiaki, Kobayashi Satoru, Nagoshi Hisao, Akiyama Masaharu, Morimoto Akira, Ida Hiroyuki, Taniwaki Masafumi
Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan.
Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
Genes Chromosomes Cancer. 2015 Jul;54(7):409-17. doi: 10.1002/gcc.22252. Epub 2015 Apr 30.
Acute lymphoblastic leukemia (ALL) occasionally develops before or after the onset of Langerhans cell histiocytosis (LCH). The mechanism of LCH developing after ALL remains unclear; thus the clonality of LCH developing during maintenance chemotherapy for T-cell ALL (T-ALL) was investigated. The T-ALL and LCH cells tested had the same T-cell receptor (TCR) gamma rearrangement. Mutation analysis of the NOTCH1 gene revealed 7213C>T (Q2405X) in exon 34 in T-ALL and LCH cells, but 5156T>C (I1719T) in exon 27 only in T-ALL. Polymerase chain reaction-restriction fragment length polymorphism analysis revealed three patterns of NOTCH1 mutations in T-ALL cells. The results suggest that the T-ALL and LCH cells were derived from a common precursor with TCR rearrangement and a single NOTCH1 mutation, rather than LCH cells developing from a minor clone of T-ALL with single NOTCH1 mutation.
急性淋巴细胞白血病（ALL）偶尔会在朗格汉斯细胞组织细胞增多症（LCH）发病之前或之后发生。ALL发病后发生LCH的机制尚不清楚；因此，对T细胞急性淋巴细胞白血病（T-ALL）维持化疗期间发生的LCH的克隆性进行了研究。所检测的T-ALL和LCH细胞具有相同的T细胞受体（TCR）γ重排。NOTCH1基因突变分析显示，T-ALL和LCH细胞外显子34中有7213C>T（Q2405X），但仅T-ALL细胞外显子27中有5156T>C（I1719T）。聚合酶链反应-限制性片段长度多态性分析揭示了T-ALL细胞中NOTCH1突变的三种模式。结果表明，T-ALL和LCH细胞来源于具有TCR重排和单个NOTCH1突变的共同前体，而不是由具有单个NOTCH1突变的T-ALL小克隆发展而来的LCH细胞。
