The importance of critically short telomere in myelodysplastic syndrome

Abstract

A few critically short telomeres trigger genomic instability regardless of average telomere length (TL). Recently, the telomere shortest length assay (TeSLA) was developed to detect critically short telomeres and measure absolute telomeres. Using TeSLA with the internally labeled biotin probe, we measured the TL of bone marrow (BM) aspirates from 52 patients with myelodysplastic syndrome (MDS). A percentage of shortest telomeres (< 1.0kb (ShTL1.0)) were calculated. ShTL1.0 was correlated to IPSS-R risk (spearmans rho = 0.35 and p = 0.0196), and ShTL1.0 and BM blast (2.61% in < 5% blast, 4.15% in 5–10% blast, and 6.80% in 10–20% blast, respectively, p = 0.0332). Interestingly, MDS patients with a shortest TL ≥ 0.787kb at the time of diagnosis showed better overall survival (OS) and progression-free survival (PFS) than patients with a shortest TL < 0.787kb in the multivariate analyses (HR = 0.13 and 0.30, p = 0.011 and 0.048 for OS and PFS, respectively). Our results clearly show the presence and abundance of critically short telomeres in MDS patients. These pathologic telomeres are associated with IPSS-R which is a validated prognostic scoring system in MDS. Furthermore, they are independent prognostic factors for OS in MDS patients. Future prospective studies are needed to validate our results.

Highlights Telomere length (TL) has been reported to be important in myelodysplastic syndrome (MDS).A novel TeSLA method demonstrated the presence and abundance of extremely short telomeres (<1.0kb) in MDS.Critically short TL rather than an average TL is associated with the IPSS-R and BM blast in MDS.The shortest TL is an independent prognostic factor for PFS and OS.Short TL should be incorporated into the risk scoring system in MDS in the future.