Assessment of Interleukin 1β Serum Level in Different Responder Groups and Stages of Chronic Myeloid Leukemia Patients on Imatinb Mesylate Therapy

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of an acquired mutation which affects the hematopoietic stem cell, leading to a striking overproduction of immature granulocytes. The first important clue to its pathogenesis the Philadelphia chromosome created by a reciprocal translocation between chromosomes 9 and 22 (t [9; 22] [q34; q11]). The development of the BCR-ABL-targeted imatinib mesylate represents a paradigm shift in the treatment of CML. Imatinib displays inhibitory activity against other kinase(s) that play a role in monocyte/macrophage development. Accordingly many studies revealed the role of cytokines in pathophysiology of myeloid neoplasia including participation of IL-1b in the pathogenesis of CML. This study designed to assess the behavior of IL-1b through newly diagnosed patients, different responders groups (optimal, suboptimal and failure cytogenetic response) and advanced stages (acceleration and crisis groups) of CML Iraqi patients whom receiving Imatinib mesylate (tyrosine kinase inhibitor), trying to elucidate the role of immunity in pathophysiology of CML disease development and treatments. In this study 96 Iraqi CML patients under imatinib mesylate treatment categorized by complete blood picture and fluorescent in situ hybridization analysis into different response groups and stages, then used an enzyme linked immunosorbent assay technique to assess serum level of IL-1b in each response group and advance stage (acceleration and transformed) of CML patients, in comparison to level in 32 healthy control subjects and 32 newly diagnosed CML. Out of 128 patients the mean serum of interleukin 1b level (pg/ ml) for the newly diagnosed, optimal responded, suboptimal responded, failure cytogenetic and advance stage of CML were 6.53 ± 3.81, 18.47 ± 4.29, 18.69 ± 3.03, 5.73 ± 2.44, and 18.10 ± 3.10, respectively. While healthy was 12.17 ± 3.44. The measurement of IL-1b before and during treatment of CML patients may contribute to the early identification of responder and non responder patients, and help in the earlier choice and/or design of alternative therapeutic strategies.

Strong inflammatory response and Th1-polarization profile in children with acute lymphoblastic leukemia without apparent infection

“…There are reports of a high concentration of various inflammatory cytokines in ALL associated with the presence of infection or in response to chemotherapy (25)(26)(27)(28). However, there are no reports of an initial inflammatory process in newly diagnosed patients with ALL without apparent infection.…”

Expression of deubiquitinase genes and inflammatory response in myeloid leukemia

“…Another study indicated the enhanced level of TNF-α in chronic leukemia and acute lymphoblastic leukemia (ALL), but not in AML (Aguayo et al, 2000). IL-6 concentration is also found higher in CLL patients than healthy individuals (Reittie et al, 1996) and the high level of IL-1β is associated with poor prognosis in CML (Matti et al, 2014). The enhanced serum levels of the cytokines IL-6, TNF-α and IL-1β was exhibited in myeloid compartment of mice lacking A20 (Matmati et al, 2011).…”

“…Several recent studies have shown that IL-6 concentration is higher in leukemia patients including CLL and AML (Reittie et al, 1996;Zhang et al, 2020). IL-1β is a potent pro-inflammatory cytokine for host defense responses to infection and injury, and high level of IL-1β is associated with poor prognosis in CML (Matti et al, 2014).…”