Abstract 3121: Gene expression signature predicts induction treatment response and clinical outcome in adult Colombian patients with acute lymphoblastic leukemia
Authors: Cruz-Rodriguez Nataly , Quijano Sandra M. , Enciso Leonardo J. , Combita Alba L. , Zabaleta Jovanny 
Published: July 2016

Background. In Colombia ALL in adults represents a public health problem because its incidence and mortality increase annually. Only 61% of Colombian adult patients with ALL achieve complete remission. The median overall survival to the disease is less than 11.3 months and the event-free survival is 7.34 months. Identification of prognostic factors in patients with ALL is crucial for the proper planning of treatment strategies and the optimal results of therapy. Our goal was to determine gene expression signatures correlated with response to therapy and to evaluate the utility of these expression patterns as predictors of risk prior to therapy of adult Colombian patients with B-ALL.

Methods. This study included 43 adult patients newly diagnosed with B-cell precursor or common B-ALL. Patients were recruited at the Colombian National Cancer Institute and Hospital Universitario San Ignacio, both in Bogota, Colombia. The leukemic blast population from diagnostic samples was separated with magnetic microbeads coated with either anti-CD19 or anti-CD34 antibodies followed by column enrichment using standard procedures and MACS (Miltenyi, Bergisch Gladbach,Germany). Total RNA from purified leukemic cells was isolated using the RNeasy Mini Kit (Qiagen) according to the manufacturer's protocols. We used microarray analysis to identify genes that distinguish poor from good response to induction treatment using differential gene expression analysis and the response group as reference and the Illumina Custom algorithm embedded in the GenomeStudio software (Illumina). The expression profile was validated by real-time PCR (RT-PCT) using TaqMan probes. The 2-ΔΔCT method was used to estimate the fold induction of each gene using GAPDH and an internal calibrator as controls. Assays were done in triplicate.

Results. We identified 442 genes differentially expressed between 22 leukemia patients who responded and 5 who did not respond to induction chemotherapeutic treatment. Hierarchical analysis with the 99 most differentially expressed genes between the two groups revealed 3 sets of patients that differed in their clinical characteristics giving these genes high prognostic clinical outcome impact capacity. We validated the expression of 7 genes by RT PCR in 43 patients and, in addition to finding a correlation with gene expression profiles, we established correlations with good and poor prognosis from the time of diagnosis.

Conclusions. Our study suggests that the response to induction treatment and clinical outcome of patients can be predicted from the onset of the disease and that gene expression profiles can be used to stratify patient risk adequately and accurately. The present study represents the first showing that gene expression profiling could become a clinically relevant tool for stratification in the early course of disease of Colombian adults B-ALL.

Citation Format: Nataly Cruz-Rodriguez, Sandra M. Quijano, Leonardo J. Enciso, Alba L. Combita, Jovanny Zabaleta. Gene expression signature predicts induction treatment response and clinical outcome in adult Colombian patients with acute lymphoblastic leukemia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3121.