Expression dynamics of the immune mediators ARG1, TBET, CIITA, IL10 and TGFB1 in chronic myeloid leukaemia patients during the first year of imatinib therapy

• Published in: Gene Vol. 813; p. 146110
• Main Authors: Toloza, María Jazmín, Bestach, Yesica, Lincango-Yupanki, Marco, Bordone, Javier, Mariano, Romina, Tarqui, Melissa, Pérez, Mariel, Aranguren, Pedro Negri, Enrico, Alicia, Larripa, Irene B., Belli, Carolina B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2022
• Subjects: Adult; Antineoplastic Agents - pharmacology; Arginase - genetics; Arginase - metabolism; Arginase-1; Biomarkers, Pharmacological - analysis; Biomarkers, Pharmacological - blood; CIITA; CML; Female; Fusion Proteins, bcr-abl - genetics; Gene Expression; Humans; Imatinib; Imatinib Mesylate - therapeutic use; Immunologic Factors - therapeutic use; Interleukin-10 - blood; Interleukin-10 - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - blood; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Male; Middle Aged; Molecular response; Nuclear Proteins - blood; Nuclear Proteins - genetics; Protein Kinase Inhibitors - pharmacology; TBET; Trans-Activators - blood; Trans-Activators - genetics; Transcriptome - genetics; Transforming Growth Factor beta1 - blood; Transforming Growth Factor beta1 - genetics; CIITA; NR; RNA; M-MLV; ELN; PMNs; Molecular response; TNF; R; ABL1; WBC; cDNA; Hb; IL10; Imatinib; CML; TGFB1; ARG1; Treg; EMR; CP; PCA; BCR; MDSCs; IL6; TKI; Arginase-1; Dx; IFNG; DNA; TBET; CTL; HC; GAPDH; NK; PCR; MHC-II
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2021.146110

•ARG1 was the only studied gene significantly elevated in CML patients at diagnosis.•ARG1 normalized to control levels at 3 months only in optimal responder patients.•TBET expression reached normal level after 12 months in both groups of patients.•CIITA expression continued downregulated during the first year of treatment.•IL10 and TGFB1 expression achieved normal levels early at 3 months in both groups. The use of tyrosine kinase inhibitors seems to restore the broadly compromised immune system described in chronic myeloid leukaemia (CML) patients at diagnosis leading to a re-activation of the effector-mediated immune surveillance. Here, we describe the expression dynamics of immune factors during the first year on imatinib therapy. Gene expression was evaluated in 132 peripheral blood samples from 79 CML patients, including 34 who were serially followed. An aliquot of the stored sample used to monitor BCR-ABL1 levels was retro-transcribed to cDNA and gene expression was quantified by real-time PCR. An elevated expression of ARG1 was observed at diagnosis, while TBET, CIITA, IL10 and TGFB1 were significantly decreased. Once on therapy, each gene displayed a particular behaviour. ARG1 normalized to control levels at 3 months only in optimal molecular responders and was identified as the major contributor to the difference among patients. TBET reached normal levels after 12 months in optimal responders and non-responders, regardless the Th1-response previously associated, and CIITA continued downregulated. IL10 and TGFB1 achieved normal levels early at 3 months in both groups, afterwards IL10 was sustained while TGFB1 was slightly increased after 1 year in responders. Our findings are in agreement with an immune re-activation after imatinib initiation; however, some immune mediators may require a longer exposition. The follow-up of novel and reliable biomarkers, such as ARG1, one of the principal mechanisms of myeloid-derived-suppressor cells to inhibit immune system, may be useful to deepen the characterization of early responder patients.