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Are PTPN11 Mutations an Independent Prognostic Factor in AML?

By: Kayci Reyer
Posted: Wednesday, December 8, 2021

According to research presented in Blood Advances, mutations in PTPN11, an RAS-signaling regulator, may prove to be an independent prognostic indicator for poor survival outcomes in patients with acute myeloid leukemia (AML). This relationship appears to be found exclusively among patients with favorable-risk cytogenetics per European LeukemiaNet and those with subclonal mutation constellations.

“The deleterious outcome in [PTPN11-mutated] patients was found to be confined to subclonal configurations of PTPN11 mutations, which are associated with a higher rate of concomitant mutations and a different mutational spectrum, as compared with PTPN11 variants in dominant clonal rank,” concluded Christian Thiede, MD, of the Universitätsklinikum Carl Gustav Carus in Dresden, and colleagues, on behalf of the Study Alliance Leukemia.

The retrospective study performed next-generation sequencing of genomic DNA samples from 1,529 adults with newly diagnosed AML. A total of 106 patients (6.93%) in dominant (36%) or subclonal (63%) configuration were found to have PTPN11 mutations. The PTPN11 mutation subgroup had an overall higher cytogenetic favorability score (57.8% vs. 39.1%) and higher white blood cell count (P = .007) versus patients with wild-type PTPN11. Mutations in PTPN11 were associated with co-mutations in NPM1 (63%), DNMT3A (37%), and NRAS (21%).

Survival outcomes were reported to be worse for patients with PTPN11 mutations. The investigators considered such mutations to be independent prognostic factors for poor overall survival (P < .001) and relapse-free survival (P = .013). Worse rates of complete remission (odds ratio = 0.46; P = .008) were also linked to PTPN11 mutations. However, patients with dominant PTPN11 did not display the same associations with poor outcomes. According to the study authors, this may be due to marked differences in the landscape of concomitant mutations in dominant versus subclonal PTPN11 mutations.

Disclosure: For full disclosures of the study authors, visit ashpublications.org.



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