Validation of clinicopathologic features of a genetic myelodysplastic syndrome classification in an independent cohort.

BACKGROUND

Current classification systems for myelodysplastic syndromes (MDS) incorporate morphologic findings, blast percentage, and some genetic features such as del(5q) and SF3B1 and TP53 mutations. A recent comprehensive molecular taxonomy proposed by the MDS-International Working Group (MDS-IWG) categorizes MDS into 16 molecular groups and two residual groups and describes associations with various clinicopathological features and differing overall survival among groups.

PURPOSE: In this study, we attempt to validate the findings described in the MDS-IWG classification in an independent cohort.

METHODS

We applied the MDS-IWG classification to 484 cases of MDS and myelodysplastic-type chronic myelomonocytic leukemia.

RESULTS

We verified numerous findings and associations described in the MDS-IWG molecular taxonomy paper, including the association of monocytosis with the bi-TET2 group, lower bone marrow blast percentage in the SF3B1 group, and higher bone marrow blast percentage in the TP53-complex and the IDH-STAG2 groups. This study confirms the poor prognosis of the EZH2-ASXL1 group despite low blast counts. Blast counts tended to affect prognosis most in the low-risk molecular groups, with little impact in the high-risk molecular groups. Within the MDS-IWG TP53-complex group, we find significant survival differences between TP53-mutated and unmutated cases, suggesting that this group is clinically and biologically heterogeneous.

CONCLUSION

The MDS-IWG molecular taxonomy of MDS is clinically applicable in routine practice and exhibits clinicopathologic and prognostic significance.