MicroRNAs and tRNA-derived fragments predict the transformation of myelodysplastic syndromes to acute myeloid leukemia

Abstract

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders of the elderly that carry an increased risk of progression to acute myeloid leukemia (AML). Since small non-coding RNAs (sRNAs), including microRNA (miRNAs), act as regulators of cellular differentiation, we hypothesized that changes to sRNAs might be implicated in the progression of MDS to AML. We conducted sRNA sequencing on three sets of patients: Group A (MDS patients who never progressed to AML); Group B (MDS patients who later progressed to an AML); and Group C (AML patients with myelodysplasia-related changes, including patients with a known preceding diagnosis of MDS). We identified five miRNAs that differentiated Groups A and B, independent of bone marrow blast percentage, including three members of the miR-181 family, as well as differential patterns of miRNA isoforms (isomiRs) and tDRs. Thus, we have identified sRNA biomarkers that predict MDS cases that are likely to progress to AML.

Keywords:

• Myeloid leukemias and dysplasias
• prognostication
• molecular genetics

Acknowledgements

This work was supported in part by the Vanderbilt CTSA grant UL1 RR024975 from NCRR/NIH (ASK). YG, SZ, and QS were supported by NIH Cancer Center Support Grant P30 CA68485. K.C.V. is supported by NIH/NHLBI HL128996, HL113039, and HL116263. This work was also supported by the American Heart Association to K.C.V. (CSA2066001).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1272680.