Absence of microsatellite instability in primary myelodysplastic syndrome

Using polymerase chain reaction (PCR), we examined a panel of 10 microsatellite markers (BAT26, BAT40, D2S123, D4S171, D8S87, D10S197, D12S89, Tp53, D18S58, PLCpr) covering nine chromosomal arms for microsatellite instability (MSI) in 29 patients with primary MDS. Bone marrow DNA was compared with corresponding constitutional DNA derived from buccal epithelial cells. Apart from BAT26 and BAT40 that were mononucleotide (poly A) repeats, the others were dinucleotide (CA) repeats. The patients comprised 10 cases of refractory anemia (RA), three cases of refractory anemia with ringed sideroblasts (RARS), nine cases of refractory anemia with excess of blasts (RAEB), four cases of refractory anemia with excess of blasts in transformation (RAEBt), and three cases of chronic myelomonocytic leukemia (CMML). Serial samples were available in seven patients, in which four showed transformation into higher disease grade or acute myeloid leukemia (AML). Genetic alterations at one locus (three at D2S123, one at D4S171) were evident in four cases, and loss of heterozygosity at Tp53 was detected in one case. Accordingly, none of the 29 patients with primary MDS nor the seven with disease progression in this study exhibited MSI. This shows that MSI may not be important in the pathogenesis or progression of MDS in contrast to other genetic mechanisms, notably recurrent chromosomal abnormalities that dysregulate the expression or function of genes controlling cell growth, differentiation and apoptosis.