Telomere length in myelodysplastic syndromes.
Boultwood J., Fidler C., Kusec R., Rack K., Elliott PJ., Atoyebi O., Chapman R., Oscier DG., Wainscoat JS.
We have studied telomere length in the bone marrow cells or the granulocyte and lymphocyte cell fractions of 54 patients with myelodysplastic syndromes (MDS) by Southern blot hybridization using the (TTAGGG)4 probe. The average telomere length expressed as the peak telomere repeat array (TRA) in the peripheral blood, or bone marrow samples obtained from a group of 21 healthy age-matched controls (26-89 years old, mean age 55), ranged between 7.5 and 9.5 kb (mean peak TRA 8.6 kb). Twenty-four patients with refractory anemia (RA) were studied; 10/24 (42%) had telomere reduction (<7.5 kb) relative to age-matched controls and the mean peak TRA was 7.5 kb (range 4.0-9.0 kb). Eleven patients with RA with excess blasts (RAEB) were studied; 5/11 (45%) had reduced telomeres relative to age-matched controls and the mean peak TRA was 7.1 kb (range 5.0-9.0 kb). Eighteen patients with MDS in transformation to AML, comprising 15 with RAEB in transformation (RAEBt) and 3 with CMML in transformation (CMMLt), were also studied. Thirteen of eighteen patients (72%) had telomere reduction relative to age-matched controls and the mean peak TRA was 6.1 kb (range 3.5-9.0 kb). Thirty-six patients included in the study had either a normal karyotype or a simple karyotype (1 karyotypic change) and 20/36 (55%) of these had telomere reduction and the mean peak TRA was 7.1 kb (range 4.3-9.0 kb); 8 patients had a complex karyotype (3 or more karyotypic changes) and 5/8 (62%) of these had telomere reduction and the mean peak TRA was 6.1 kb (range 3.5-9.0 kb). We conclude, firstly that there is heterogeneity of telomere length in MDS and that this is observed throughout the spectrum of FAB-subtypes. Secondly, these data show that a marked reduction in telomere length in MDS if often associated with leukemic transformation and with the presence of complex karyotypic abnormalities.