THE ABUNDANCE OF CYTOTOXIC CELLS IN THE BONE MARROW TUMOR MICROENVIRONMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS IS ASSOCIATED WITH SPECIFIC CLINICAL AND TRANSCRIPTOMIC FEATURES

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

Mar del Plata

Congreso; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2022

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA

Acute lymphoblastic leukemia (ALL) is characterized by bone marrow immature lymphoid blasts overproduction and is the most incident pediatric cancer worldwide. Although overall survival and treatment efficacy has increased in recent decades, some patients develop treatment-related acute toxicity and about 15-30% of patients relapse. Whether the components of the tumor microenvironment (TME) can contribute to the clinical heterogeneity observed in patients is yet to be deciphered. In this work, we aimed at characterizing the immune components of the TME in ALL by gene expression analysis and assess its prognostic value. RNA-seq was performed in bone marrow aspirates from Argentinian pediatric ALL patients at diagnosis (N=32). MIXTURE deconvolution method was used to estimate the proportion of immune cells. CD4+ T cells proportions were increased in patients that died or relapsed (p-val=5.6E-4). Next, we calculated a “cytolytic score” (CS) based on the expression of 5 specific genes for cytotoxic T lymphocytes and Natural Killer cells by RNA-seq and performed validation by RT-qPCR. Results showed that B cell proportions correlated with blasts percentage at diagnosis by blood smear (Spearman rho=0.628, p-val95% agreement (Bland-Altman analysis). CX3CR1 (adj.p-val