Short Dysfunctional Telomere is Highly Predictive of Dismal Outcome in MDS but Not in AML Patients

Abstract

Background: A trigger for initiation the clonal hematopoietic stem cells disorders could be short telomere length, probably due to chromosomal instability. The relationship between relative telomere length (RTL) and the two linked hematological stem cell disorders, myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), is still unclear.

Materials and Methods: We evaluated the role of RTL in MDS (n=96) and AML (n=130) at the time of diagnosis using a real time quantitative polymerase chain reaction (RT-PCR) technique. The median value of RTL (1) was set as the cutoff for statistical comparison. Overall survival (OS) is defined as the time from diagnosis to death or last follow-up.

Results: RTL was significantly longer in both MDS and AML cases versus control (p<0.0001) and was significantly longer in MDS versus AML cases (p =0.03). RTL correlated negatively with age in MDS (p <0.0001) but not in AML cases. RTL was also significantly shorter in MDS cases with pancytopenia and poor risk cytogenetics (p < 0.0001 for each) and short RTL was significantly associated with inferior survival (p = 0.007), while RTL showed no significant impact on OS in AML cases. Moreover, short RTL retained independent prognostic value in multivariate analysis (HR= 3.42 [95% CI, 8.97-19.35], p = 0.004).

Conclusion: RTL showed an association with both AML and MDS; however, short RTL was an independent poor prognostic factor in MDS patients only.