Tasak T, Lee S, Spira S, Takeuchi S, Hatta Y, Nagai M, Takahara J, Koeffler H P
Department of Medicine, Ceders-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Leuk Res. 1996 Feb;20(2):113-7. doi: 10.1016/0145-2126(95)00119-0.
Microsatellites are highly polymorphic, short-tandem repeat sequences dispersed throughout the genome. Instability of these repeat sequences at multiple gentic loci may result from mismatch repair errors and occur in hereditary nonpolyposis colorectal cancer and several other sporadic cancers, including chronic myelocytic leukemia as it progresses to blastic crisis. We investigated whether genetic instability occurred as myelodysplasia progressed to acute myelocytic leukemia. To this end, we studied microsatellite instability in 20 patients with myelodysplastic syndrome (MDS). These included five patients with refractory anemia (RA), three with refractory anemia with ringed sideroblast (RARS), nine with refractory anemia with excess blasts (RAEB) and three with chronic myelomonocytic leukemia (CMML). All of these patients transformed to acute myelocytic leukemia (AML) of various subtypes: three patients with M1, 11 with M2 and six patients with M4 (according to FAB classification). The DNA from both the MDS and AML phases of their disease was analyzed at 16 loci, and only four microsatellite instabilities were found in the 240 paired samples (1.6%) analyzed. These results indicate that mismatch repair errors such as microsatellite instability are not important in the evolution of MDS to AML.
微卫星是高度多态性的短串联重复序列，分散于整个基因组中。这些重复序列在多个基因位点的不稳定性可能源于错配修复错误，发生于遗传性非息肉病性结直肠癌及其他几种散发性癌症，包括慢性粒细胞白血病进展为急变期时。我们研究了骨髓增生异常综合征进展为急性髓细胞白血病时是否会发生基因不稳定。为此，我们研究了20例骨髓增生异常综合征（MDS）患者的微卫星不稳定性。其中包括5例难治性贫血（RA）患者、3例环形铁粒幼细胞性难治性贫血（RARS）患者、9例原始细胞增多的难治性贫血（RAEB）患者和3例慢性粒单核细胞白血病（CMML）患者。所有这些患者均转化为不同亚型的急性髓细胞白血病（AML）：3例M1型、11例M2型和6例M4型（根据FAB分类）。对其疾病的MDS期和AML期的DNA在16个位点进行分析，在所分析的240对样本中仅发现4例微卫星不稳定性（1.6%）。这些结果表明，诸如微卫星不稳定性之类的错配修复错误在MDS向AML的演变中并不重要。
