The Study Of The Relationship Between Chronic Myeloid Leukemia And Microsatellite Instabilities

Objective : To study the instabilities of 5 microsatellite markers on chromosome 8,9 and 17 in chronic myeloid leukemia (CML), and to investigate the possible genetic abnormalities that are associated with the pathogenesis and progression of CML and the significance of these abnormalities in the acute transformation of CML.Methods : We have chosen 37 CML cases, including 27 chronic phase (CP), 5 accelerated phase (AP) and 5 blast crisis (BC) cases . Bone marrow and oral mucosa cell DNA samples of these patients were examined using 5 microsatellite markers on chromosome 8, 9 and 17 (D8S559 on 8q22, D8S555 on 8q24, D9S67 on 9q34, TP53 A1/A2 and AFMal27xg9 on 17pl3) for microsatellite instability (MSI) including loss of heterozygosity (LOH) by PCR amplification, polyacrylamide gel electrophoresis (PAGE) and argentine dye comparing with 20 AML cases, 20 benign hemopathy cases and S normal controls.Results : MSI in at least one microsatellite site were found in 21 of 37 CML cases (56.8%). Nine of 37 CML cases (24.3%) show MSI in more than one sites. The MSI incidences of those five sites D8S555, D8S559, D9S67, TP53A1/A2 and AFMal27xg9 were 19.0% (7/37), 27.0% (10/37), 10.8% (4/37), 10.8% (4/37), 29.7% (11/37) in total CML cases and 7.4% (2/27), 40.0% (2/5), 60.0% (3/5); 22.2% (6/27), 20.0% (1/5), 60.0% (3/5); 14.8% (4/27), 0% (0/5), 0% (0/5); 14.8% (4/27), 0% (0/5), 0% (0/5); 29.6% (8/27), 40.0% (2/5), 20.0% (1/5) in CP, AP, BC cases respectively. In D8S555 the frequency of MSI in CML advanced phase (AP and BC ) cases was higher than that in CML CP cases (p < 0.01) and in the other 4 sites the frequencies of MSI were not statistical different among CML phases (p > 0.05). In AFMa127xg9 CML cases show high incidence of LOH. MSI in at least one microsatellite site were found in 11 of 20 AML cases (55.0%). Four of 20 AML cases (20.0%) show MSI in more than one sites.The MSI incidences of those five sites in AML cases were 25.0% (5/20), 30.0% (6/20), 5.0% (1/20), 5.0% (1/20), 20.0% (4/20). There was no statistical difference in frequencies among those five sites between CML and AML cases (p > 0.05). No abnomalities were detected in benign hematopathy cases and normal controls.Conclusions : The high incidence of microsatellite instabilities in D8S555, D8S559 on chromosome 8 and in AFMa127xg9 on chromosome 17 indicates that these abnomalities may play a role in the initiation and development of CML. The statistical difference between CML chronic phase (CP) and advanced phase (AP and BC) in D8S555 reveals that the instability of this site may be involved in the transformation of CML from chronic phase to advanced phase and that some genes may contribute to the progression of CML. The high incidence of LOH in AFMal27xg9 suggests that...