Cytokine and arginase-1 expression dynamics in patients with chronic myeloid leukemia reveals early molecular response to imatinib

BESTACH, YESICA; TOLOZA, MARIA JAZMIN; ENRICO, ALICIA; LARRIPA, IRENE; BELLI, CAROLINA

Amsterdam

Congreso; 24th Congress of the European Hematology Association; 2019

European Hematology Association

Introduction Imatinib remains as the preferred tyrosine kinase inhibitor (TKI) to treat chronic myeloid leukaemia (CML) patients. Besides its direct action targeting BCR-ABL1, TKI therapy may also influence the anti-tumour response. A broadly compromised immune system has been described at time of diagnosis supporting for a suppression of anti-CML immune responses. These abnormalities include an expansion of the suppressive immune cell populations, myeloid derived suppressor cells (MDSCs) and regulatory T cells (Treg), and dysfunctional effector NK- and T-immune responses. On TKI treatments, CML patients seem to re-activate their immune system restoring the effector-mediated immune surveillance.Objective To describe TNF, IFNG, IL6, IL10, TGBF1, and ARG1 gene expression dynamic regarding molecular response to imatinib, since previous studies were designed by different approaches, criteria for timing and longitudinally studies are scare or missing.Material and methods We analysed 106 peripheral blood samples of 64 CML patients, with multiple samples of 34 serially followed, and 26 of healthy donors. Were included patients at diagnosis (n=23) and on imatinib 400 mg at 3 months (n=41), 6 months (n=42) classified according to the molecular response. An aliquot of the stored sample used to monitor BCR-ABL1 level was retro-transcribed to cDNA and TNF, IFNG, IL6, IL10, TGFB1 and ARG1 gene expression was quantified by PCR real time.Results For patients at diagnosis, the expression of TNF, IFNG, IL6, IL10 and TGFB1 was significantly decreased when compared with healthy controls (Mann-Whitney test p=0.0336, p