Department of Molecular Oncology and Leukemia Program Project, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Cancer Sci. 2021 Apr;112(4):1383-1389. doi: 10.1111/cas.14852. Epub 2021 Mar 2.
Revertant (somatic) mosaicism is a spontaneous correction of a causative mutation in patients with congenital diseases. A relatively frequent event, revertant mosaicism may bring favorable outcomes that ameliorate disorders, and is therefore called "natural gene therapy." However, it has been revealed recently that "overcorrection" of inherited bone marrow failure in patients with sterile alpha motif domain containing 9 (SAMD9)/9L syndromes by revertant mosaicism induces myelodysplastic syndrome (MDS) with monosomy 7 that occasionally proceeds to acute myelogenous leukemia (AML). In this review, we interpret very complex mechanisms underlying MDS/AML in patients with SAMD9/9L syndromes. This includes multiple myeloid tumor suppressors on the long arm of chromosome 7, all of which act in a haploinsufficient fashion, and a difference in sensitivity to interferon between cells carrying a mutation and revertants. Overcorrection of mutants by somatic mosaicism is likely a novel mechanism in carcinogenesis.
回复（体）嵌合体是先天性疾病患者中致病突变的自发纠正。这是一个相对频繁的事件，回复嵌合体可能会带来有利的结果，改善疾病，因此被称为“自然基因治疗”。然而，最近发现， sterile alpha motif domain containing 9（SAMD9）/9L 综合征患者的遗传性骨髓衰竭的“过度纠正”通过回复嵌合体诱导伴有 7 号单体性的骨髓增生异常综合征（MDS），偶尔进展为急性髓系白血病（AML）。在这篇综述中，我们解释了 SAMD9/9L 综合征患者 MDS/AML 的非常复杂的机制。这包括 7 号染色体长臂上的多个髓系肿瘤抑制因子，它们都以单倍不足的方式发挥作用，以及突变细胞和回复细胞对干扰素的敏感性差异。体细胞嵌合体对突变体的过度纠正可能是致癌作用的一种新机制。
