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

Abstract

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.