Among patients with myeloid neoplasms including acute myeloid leukemia (AML), IDH2 R172 mutations (mR172) appear to be linked with improved overall survival, and moreover represent a distinct clinical disease subtype, according to research published in the American Journal of Clinical Pathology.

IDH1 and IDH2 mutations are relatively common mutations known in the AML space, as well as among patients with solid tumors including gliomas. For this retrospective study, researchers explored disease features among patients with AML with mR172 to determine whether this mutation is a hallmark of a distinct disease subtype.

The authors contrasted clinical samples and data from 39 patients with IDH2 R140 (mR140) or mR172. All patients had a myeloid neoplasm and increased blasts.

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Analysis showed that mR172 was linked with lower leukocyte counts and bone marrow cellularity; moreover, blasts in samples with mR172 were more likely to be invaginated, have cleaved nuclei, and express CD34, HLA-DR, CD117, and CD13. Patients with mR172 were also more likely to have mutations in genes linked with myelodysplasia and/or an adverse karyotype.

Surprisingly, however, patients with mR172 had improved overall survival, compared with non-mR172 cases (P =.01); this finding was validated in an independent dataset.

“In an era of targeted therapy, with IDH1 and IDH2 small-molecule inhibitors receiving FDA approval and entering routine clinical use, resolution of the clinicopathologic features and survival expectations associated with distinct genetic subtypes of IDH-mutated myeloid neoplasia is imperative to aid in appropriate classification and prognostication, as well as guide appropriate therapy,” the authors wrote in their report.


Davis AR, Canady BC, Aggarwal N, Bailey NG. Clinicopathologic features of IDH2 R172-mutated myeloid neoplasms. Am J Clin Pathol. Published online March 22, 2023. doi:10.1093/ajcp/aqad019