Abnormal levels of proinflammatory cytokines in serum and monocyte cultures from patients with chronic myeloid leukemia in different stages, and their role in prognosis

Abstract

Interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), primarily monocyte-derived cytokines, form a group of proinflammatory cytokines with related and overlapping spectra of activities. The role of these cytokines in chronic myeloid leukemia (CML) has been investigated. A distinctive pattern of cytokine secretion has been found in chronic myeloid leukemia in chronic phase (CML-CP), in blastic crisis (CML-BC) and in normal subjects. Serum IL-6 levels in CML-CP and CML-BC were significantly raised compared with normal controls (p = 0.0026 for CML-CP and p = 0.0011 for CML-BC). IL-6 was significantly elevated in blastic crisis of CML (103.5 +/- 20.77 pg ml-1) compared with CML-CP (37.35 +/- 10.88 pg ml-1; p = 0.014). IL-6 serum levels were found to correlate significantly with peripheral blood monocyte counts and bone marrow blast and basophil counts. We have analysed monocyte/macrophage function with respect to their ability to produce IL-1, IL-6 and TNF-alpha, spontaneously as well as in response to LPS, in comparison with normal controls. A direct correlation of IL-6 levels in unstimulated and stimulated cultures with bone marrow blast and basophil counts has been observed. From these results it is inferred that the monocyte function is impaired in CML patients, and the cytokine secretion is deficient. Our limited data suggest that serum IL-6 levels may play an important role as a prognostic marker for CML.

Leptin Reverts Pro-Apoptotic and Antiproliferative Effects of α-Linolenic Acids in BCR-ABL Positive Leukemic Cells: Involvement of PI3K Pathway

“…Lipid accumulation in myeloid cells has previously been noted in some pathological conditions such as atherosclerosis [32] and asthma [33]. In cancer [18]–[19], this accumulation seems to protect cells from microenvironmental cytotoxins [34]–[35] and to induce inflammatory response [36]–[38] frequently observed in the BM of CML patients [39] and associated with reduced proliferation [34], [40]–[41].…”

Pro-inflammatory cytokines: Emerging players regulating HSC function in normal and diseased hematopoiesis

“…Notably, elevated IL-6 levels are found in CML patients (Anand et al, 1998). Similar IL-6 overproduction was traced to myeloid cells using a tetracycline-inducible transgenic BCR/ABL ( BA Scl-tTA ) mouse model that reproduces the hematological features of human CML (Reynaud et al, 2011).…”

“…While the integration of such signals with hematopoietic output may promote effective host defense in acute conditions, prolonged exposure to them can be detrimental to HSC function. Indeed, hematopoietic failure associated with overproduction of pro-inflammatory cytokines is often a feature of chronic inflammatory diseases, hematological malignancies and bone marrow failure syndromes (Anand et al, 1998, Ishihara and Hirano, 2002, Braun et al, 2013). Thus, identifying how inflammation regulates HSC fate and function in normal and disease conditions represents a crucial frontier for our understanding and treatment of chronic inflammation and blood disorders.…”

Prognostic role of the lymphocyte-to-monocyte ratio in colorectal cancer

“…[6,17] Several proinflammatory cytokines, secreted from monocytes, are associated with poor prognosis in cancer patients, such as tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1. [18] Besides, tumor-associated macrophages, derived from circulating monocytes, have a role in suppressing adaptive immunity and promoting angiogenesis, invasion, and migration. [19] From the above, a decreased LMR could generate a favorable immune microenvironment that promotes cancer development.…”