CHARACTERIZATION OF CD20 ISOFORM DIVERSITY IN PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA: POTENTIAL IMPLICATIONS FOR RITUXIMAB TREATMENT

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

Mar del Plata

Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2023

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

Acute lymphoblastic leukemia (ALL) is characterized by the overproduction of immature lymphoid blasts in the bone marrow and is the most incident pediatric cancer worldwide. Numerous advances have been achieved in the treatment. Rituximab, an anti-CD20 monoclonal antibody, will be incorporated into the multinational clinical protocol ALL IC-BFM 2020, of which Argentina is a participating member. However, the existence of different MS4A1 (CD20 coding gene) transcripts might have potential implications in treatment response. Our study aimed to characterize and quantify the CD20 isoforms in ALL patients. To accomplish this goal, we performed RNA-seq on bone marrow aspirates collected at diagnosis from Argentinian pediatric ALL patients (n=31). The analysis of CD20 transcript expression revealed high heterogeneity among patients, both in terms of total gene levels as well as in the absolute and relative abundance of transcripts. We found high levels of ENST00000532073 transcript were associated with a lower chance of event-free survival (Hazard Ratio=6.45, Cox p=0.01; Log-rank=0.02). We also performed a bioinformatics analysis using bone marrow samples of ALL patients (TARGET, n=207) and healthy donors (GTEx, n=70). Of all CD20 transcripts, only ENST00000532073 was detected in healthy donors, and with lower levels (TPM