Serum Chemokine-release Profiles in AML-patients Might Contribute to Predict the Clinical Course of the Disease

Abstract

In cancer or hematologic disorders, chemokines act as growth-or survival factors, regulating hematopoiesis and angiogenesis, determining metastatic spread and controlling leukocyte infiltration into tumors to inhibit antitumor immune responses. The aim was to quantify the release of CXCL8, −9, −10, CCL2, −5, and IL-12 in AML/ MDS-pts' serum by cytometric bead array and to correlate data with clinical subtypes and courses. Minimal differences in serum-levels subdivided into various groups (e.g. age groups, FAB-types, blastproportions, cytogenetic-risk-groups) were seen, but higher release of CXCL8, −9, −10 and lower release of CCL2 and −5 tendentially correlated with more favorable subtypes (<50 years of age, <80% blasts in PB). Comparing different stages of the disease higher CCL5-release in persisting disease and a significantly higher CCL2release at relapse were found compared to first diagnosispointing to a change of 'disease activity' on a chemokine level. Correlations with later on achieved response to immunotherapy and occurrence of GVHD were seen: Higher values of CXCL8, −9, −10 and CCL2 and lower CCL5-values correlated with achieved response to immunotherapy. Predictive cut-off-values were evaluated separating the groups in 'responders' and 'non-responders'. Higher levels of CCL2 and −5 but lower levels of CXCL8, −9, −10 correlated with occurrence of GVHD. We conclude, that in AML-pts' serum higher values of CXCL8, −9, −10 and lower values of CCL5 and in part of CCL2 correlate with more favorable subtypes and improved antitumor'-reactive function. This knowledge can contribute to develop immune-modifying strategies that promote antileukemic adaptive immune responses.

IL-1β Induces SOCS2 Expression in Human Dendritic Cells

“…A recent study suggests that IL-8 as well as RANTES may also be valuable predictive markers in AML. The latter study reports that high serum IL-8 and low RANTES levels are correlated with a more favorable prognosis and may also be associated with a higher probability for AML patients to respond to immunotherapy [31]. In accordance, we detected significantly increased secretion of IL-8, but decreased RANTES expression in SOCS2-silenced, IL-1β-stimulated DCs.…”

Macrophages in Acute Myeloid Leukaemia: Significant Players in Therapy Resistance and Patient Outcomes

“…Moreover, the level of CCL2 is a prognostic marker for AML, with higher serum levels of this chemokine detected in untreated AML individuals possessing unfavourable cytogenetics when compared to patients with favourable cytogenetics ( Mazur et al, 2007 ). High CCL2 serum levels are also predictive of poor clinical outcomes in AML patients ( Merle et al, 2019 ). Elevated serum levels of CHI3L1, in newly diagnosed AML patients, have also been associated with inferior survival at 1 and 12 months post diagnosis ( Bergmann et al, 2005 ).…”

LINC01255 combined with BMI1 to regulate Human Mesenchymal Stromal Senescence and Acute myeloid leukemia cell proliferation through repress the transcription of MCP-1

“…MCP-1 is associated with a poor prognosis in patient with certain cancers, such as breast cancer. Also, MCP-1 can promote lung metastasis or glioblastoma and tumor growth [41]. In addition, MCP-1 is associated with senescence of UCB-MSC through activating p53/p21 signaling pathway.…”

“…The monocyte chemoattractant protein-1 (MCP-1/CCL2) is a member of the C-C chemokine family, and a potent chemotactic factor for monocytes. It is also expressed in tumor cells, B-ALL, AML cells and tumor stroma cells, which are mainly secreted by inflammatory cells and endothelial cells [41][42][43][44]. MCP-1 is associated with a poor prognosis in patient with certain cancers, such as breast cancer.…”