MOLECULAR AND IMMUNE LANDSCAPE OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA IN ARGENTINE PATIENTS FROM THE ALLIC-GATLA-2010 PROTOCOL

RUIZ, MARÍA SOL; AVEDAÑO, DANIEL; GOMEZ MERCADO, IGNACIO; ABBATE, MERCEDES; RICCHERI, CECILIA; VAZQUEZ, ELBA; GUERON, GERALDINE; COTIGNOLA, JAVIER

Otawa

Congreso; 55th Congress of the International Society of Paediatric Oncology; 2023

International Society of Paediatric Oncology

Background and aims: Acute Lymphoblastic Leukemia (ALL) is a genetically heterogeneous entity. Its molecular features can be prognostic and set the basis for therapeutic decisions. We aimed to find clinically relevant biological signatures using a comprehensive molecular characterization of childhood B-ALL that includes features from both the leukemic cells and the tumor microenvironment (TME). Methods: we studied single nucleotide variants (SNVs), fusion genes and CD20 isoform abundance in 39 patients recruited under the ALLIC-GATLA-2010 protocol. We analyzed the transcriptome of bone marrow samples at time of diagnosis. RNAmut was used to evaluate SNVs/InDels in 114 genes and 79 fusion genes. Discovery of fusion genes was complemented with STAR-Fusion. Variants were filtered based on an in-house pipeline. Quantification of isoforms was performed using Salmon. The immune component of the TME was estimated by MIXTURE, and the abundance of cytotoxic cells was assessed by a gene expression-based cytolytic score. Results: we identified 20 SNVs/InDels in 14/33 patients. We found variants in CREBBP, CSF3R, ETV6, TP53, ATM and DUX4 that were not previously described in ALL. We also detected 7 previously reported and two novel fusion genes in 11/33 patients. CX3CR1, HAVCR2, CCL4, XCL2 and IL7 RNA levels were increased in patients with high vs low cytolytic score (p-val