Abstract 2951: Gene expression profiling identifies new adult "triple-negative" acute lymphoblastic leukemia (ALL) subgroups
Authors: Ferrari Anna , Vitali Silvia , Robustelli Valentina , Rorà Andrea Ghelli Luserna Di , Righi Simona , Papayannidis Cristina , Marconi Giovanni , Imbrogno Enrica , Santoro Alessandra , Hernández-Rivas J M. , Baldazzi Carmen , Abbenante Maria Chiara , Paolini Stefania , Testoni Nicoletta , Castellani Gastone , Sabattini Elena , Cavo Michele , Remondini Daniel , Martinelli Giovanni 
Published: August 2018

Background: Although there has been remarkable progress, there is a need to improve the molecular dissection of subtypes, identifying genetic alterations that predict the risk of treatment failure and developing novel and targeted therapies. B-ALL patients (pts) that do not have the most recurrent adult rearrangements (BCR-ABL1 t(9;22); TCF3-PBX1 t(1;19); MLL-AF4 t(4;11)) are collectively referred to as “triple negative” (Ph-/-/-) ALL.

Aims: Biologic characterization of Ph-/-/- ALL considering CRLF2 overexpression event (that represents near to 57% of B-ALL; Roberts KG, J Clin Oncol 2016), in in order to define and assess biomarkers in this subgroup to test new drugs.

Patients and Methods: Gene Expression Profiling (GEP; HTA 2.0 Affymetrix) was performed on 51 Ph-/-/- ALL, 25 B-ALL Ph+ at different time point of the disease and on 7 mononuclear cell of healthy donors. Data were normalized and analyzed with the Expression Console and the Transcriptome Analysis Console (TAC) Software (Affymetrix). Successively we cluster triple-negative GEP data with our validated pipeline, based in a top ten gene list.

Results: Comparing GEP of Ph-/-/- and Ph+ to donors we found some shared top upreg genes to focus on (e.g., EBF1, CD19, BLNK, PDLIM1, PXDN, NAV1, CTGF, LEF1, CD200, CRLF2). In triple-negative ALL GEP top upreg gene analysis we identify a well-defined 2-clusters-subdivision (Gr1 and Gr2). Furthermore, a third group , in the Gr1, can be identified by the algorithm without ambiguous assignments. The Gr2 is characterized by CTGF, CRLF2 and CD200 overexpression and it represents 11.3% of all B-ALL. Two groups t-test has been performed between Ph+ and the isolated subgroups of Ph- to determine the similarity of these two groups to Ph+. The Gr2 GEP is similar to Ph+ one.

Conclusions: We identified a new signature, related to CRLF2 high expression, to classify Ph-/-/- ALL B-based on 10 genes. Gr2 represents 11.3% of all B-ALL and it is characterized by high expression of three main genes: CRLF2, CTGF and CD200. Gr1 represents 46% of all B-ALL. Gr2 GEP similarity to Ph+ one, suggests that this Gr2 could contain Ph-like pts. This new Ph-/-/- subclassification identifies new potential therapeutic targets to test as a single agent or in combination.

ELN, AIL, AIRC, project Regione-Università 2010-12 (L. Bolondi), FP7 NGS-PTL project, HARMONY project, Fondazione del Monte BO e RA project.

Citation Format: Anna Ferrari, Silvia Vitali, Valentina Robustelli, Andrea Ghelli Luserna Di Rorà, Simona Righi, Cristina Papayannidis, Giovanni Marconi, Enrica Imbrogno, Alessandra Santoro, J M. Hernández-Rivas, Carmen Baldazzi, Maria Chiara Abbenante, Stefania Paolini, Nicoletta Testoni, Gastone Castellani, Elena Sabattini, Michele Cavo, Daniel Remondini, Giovanni Martinelli. Gene expression profiling identifies new adult "triple-negative" acute lymphoblastic leukemia (ALL) subgroups [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2951.