High expression of ETS2 predicts poor prognosis in acute myeloid leukemia and may guide treatment decisions

Abstract

Background ETS2 is a downstream effector of the RAS/RAF/ERK pathway, which plays a critical role in the development of malignant tumor. However, the clinical impact of ETS2 expression in AML remains unknown. MethodsIn this study, we evaluated the prognostic significance of ETS2 expression using two relatively large cohorts of AML patients.ResultsIn the first cohort, compared to low expression of ETS2 (ETS2 low), high expression of ETS2 (ETS2 high) showed significant shorter OS, EFS and RFS in the current treatments including the allogeneic HCT group (n = 72) and the chemotherapy group (n = 100). Notably, among ETS2 high patients, those received allogeneic HCT had longer OS, EFS and RFS than those with chemotherapy alone (allogeneic HCT, n = 39 vs. chemotherapy, n = 47), but treatment modules play insignificant role in the survival of ETS2 low patients (allogeneic HCT, n = 33 vs. chemotherapy, n = 53). Moreover, gene/microRNA expression data provides insights into the biological changes associated with varying ETS2 expression levels in AML. The prognostic value of ETS2 was further validated in the second AML cohort (n = 329).ConclusionsOur results indicate that ETS2 high is a poor prognostic factor in AML and may guide treatment decisions towards allogeneic HCT.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1260-2) contains supplementary material, which is available to authorized users.

Identification of new therapeutic targets inCRLF2-overexpressing B-ALL through discovery of TF-gene regulatory interactions

“…As a result, we defined 36 significant TF regulators predicted to regulate 2,410 gene targets from the inferred B-ALL regulatory network previously described, with the number of targets for each TF shown in Supplemental Fig 4c . We note that many TFs (FOXM1 38 , ETS2 39, 40 , BCL11A 41 , FOXO1 42 , etc.) with significantly altered activity are implicated in cancer and could therefore potentially contribute to tumorigenesis in CRLF2 -High B-ALL patients.…”

“…The network-driven approach also identified a number of significant TF regulator motifs including ETS2 40 , FOXO1 42 , EGR1 82 , and FOXM1 38, 55, 56 , which are implicated in hematological malignancies. FOXM1 could be an important regulator in CRLF2 -overexpressing cells due to its crucial role in cell proliferation and its implication in various cancer types, as described earlier.…”

Identification of an Immune-Related Gene Signature Based on Immunogenomic Landscape Analysis to Predict the Prognosis of Adult Acute Myeloid Leukemia Patients

“…Dysregulation of these pathways were closely associated with AML progression. Liu et al reported that the high level of expression of ETS2 predicted the unfavorable prognosis for AML patients (31). ENO1 functions as a glycolytic enzyme and was found to be upregulated in the AML samples (32).…”

PIM-1 mRNA expression is a potential prognostic biomarker in acute myeloid leukemia

“…Besides, Goldberg et al studied that PIM-1 and the RAS pathway are potential therapeutic targets of high-risk leukemia [ 34 ]. In addition, ETS2, a downstream effector of the RAS/RAF/ERK pathway, the same as PIM-1, which plays a crucial role in cell growth and Fu et al also reported that high expression of ETS2 predicted poor prognosis in acute myeloid leukemia [ 35 , 36 ]. This illustrates that our finding may be relevant to these studies.…”