A 4-gene expression prognostic signature might guide post-remission therapy in patients with intermediate-risk cytogenetic acute myeloid leukemia

Abstract

In intermediate-risk cytogenetic acute myeloid leukemia (IRC-AML) patients, novel biomarkers to guide post-remission therapy are needed. We analyzed with high-density arrays 40 IRC-AML patients who received a non-allogeneic hematopoietic stem-cell transplantation-based post-remission therapy, and identified a signature that correlated with early relapse. Subsequently, we analyzed selected 187 genes in 49 additional IRC-AML patients by RT-PCR. BAALC, MN1, SPARC and HOPX overexpression correlated to refractoriness. BAALC or ALDH2 overexpression correlated to shorter overall survival (OS) (5-year OS: 33 ± 8.6% vs. 73.7 ± 10.1%, p = .006; 32 ± 9.3% vs. 66.4 ± 9.7%, p = .016), whereas GPR44 or TP53INP1 overexpression correlated to longer survival (5-year OS: 66.7 ± 10.3% vs. 35.4 ± 9.1%, p = .04; 58.3 ± 8.2% vs. 23.1 ± 11.7%, p = .029). A risk-score combining these four genes expression distinguished low-risk and high-risk patients (5-year OS: 79 ± 9% vs. 30 ± 8%, respectively; p = .001) in our cohort and in an independent set of patients from a public repository. Our 4-gene signature may add prognostic information and guide post-remission treatment in IRC-AML patients.

Keywords:

• AML
• GEP
• intermediate-risk

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1422859.

Additional information

Funding

This research is supported by grants from Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III (ISCIII) N-2004-FS041085, PI080158, PI13/00999, PI014/00450, PIE15/00028, RETICS RD06/0020/0004, RD12/0036/007, PI16/01027 and AGAUR 2014-SGR-1281. Marina Díaz-Beyá is supported by ISCIII (Río Hortega CM13/00205).