A 4-Gene Expression Prognostic Signature Might Guide Post-Remission Therapy In Patients With Intermediate-Risk Cytogenetic Acute Myeloid Leukemia

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.