Tomonaga M, Tomonaga Y, Kusano M, Ichimaru M
Br J Haematol. 1984 Sep;58(1):53-60. doi: 10.1111/j.1365-2141.1984.tb06058.x.
Serial haematopathological and cytogenetic studies disclosed three distinct clinical phase in a case of refractory anaemia (RA), a subtype of myelodysplastic syndrome (MDS; FAB group, 1982): first, chronic MDS phase (1 year 10 months) with karyotypic abnormality (45, XY, --7) (Clone I); second, hypo-aplastic phase concurrent with first clonal evolution (45, XY, --7, 12p--) (Clone II); third, acute myelomonocytic leukaemia phase (6 months) with second clonal evolution (45, XY, --7,t (1q --; Bq+), Bq --, 12p --) (Clone III). In the second phase the bone marrow became almost aplastic as Clone II expanded progressively, indicating simultaneous occurrence in Clone II stem cells of growth advantage for self-renewal function over Clone I and normal stem cells, and arrest of differentiation. These observations support the hypothesis that leukaemic change in MDS, at least in RA, occurs by stepwise clonal evolution(s), not by progressive arrest of differentiation in original MDS clone.
对一名难治性贫血（RA）患者（骨髓增生异常综合征（MDS；FAB分类，1982）的一种亚型）进行的系列血液病理学和细胞遗传学研究揭示了三个不同的临床阶段：第一，慢性MDS阶段（1年10个月），伴有核型异常（45，XY，-7）（克隆I）；第二，低增生阶段，同时伴有首次克隆演变（45，XY，-7，12p-）（克隆II）；第三，急性粒单核细胞白血病阶段（6个月），伴有第二次克隆演变（45，XY，-7，t（1q-；Bq+），Bq-，12p-）（克隆III）。在第二阶段，随着克隆II逐渐扩增，骨髓几乎呈再生障碍状态，这表明在克隆II干细胞中，自我更新功能的生长优势相对于克隆I和正常干细胞同时出现，且分化停滞。这些观察结果支持了这样一种假说，即MDS中的白血病变化，至少在RA中，是通过逐步的克隆演变发生的，而不是通过原始MDS克隆中的分化进行性停滞发生的。
