Circulating cytokines and small molecules follow distinct expression patterns in acute myeloid leukaemia

Abstract

Background:Although aberrant expression of cytokines and small molecules (analytes) is well documented in acute myeloid leukaemia (AML), their co-expression patterns are not yet identified. In addition, plasma baselines for some analytes that are biomarkers for other cancers have not been previously reported in AML.Methods:We used multiplex array technology to simultaneously detect and quantify 32 plasma analyte (22 reported analytes and 10 novel analytes) levels in 38 patients.Results:In our study, 16 analytes are found to be significantly deregulated (13 higher, 3 lower, Mann–Whitney U-test, P-value <0.005), where 5 of them have never been reported before in AML. We predicted a seven-analyte-containing multiplex panel for diagnosis of AML and, among them, MIF could be a possible therapeutic target. In addition, we observed that circulating analytes show five co-expression signatures.Conclusions:Circulating analyte expression in AML significantly differs from normal, and follow distinct expression patterns.

Phase Ib Study of Glasdegib, a Hedgehog Pathway Inhibitor, in Combination with Standard Chemotherapy in Patients with AML or High-Risk MDS

“…These analyses focused on cytokines, as previous studies had demonstrated that aberrant cytokine expression is nearly universal in AML/MDS and that some cytokines exhibit potential prognostic and/or predictive value or are implicated in AML/MDS pathobiology (including IL6, IL8, IL10, VEGF, and TNFa; refs. [22][23][24][25][26][27]. Moreover, Hh pathway signaling has been shown to modulate the expression of proinflammatory molecules such as TNFa, IL1b, and IL6 (28).…”

The cytokine network in acute myeloid leukemia

“…Studies evaluating pro-and antiinflammatory cytokine and growth factor levels in serum revealed that GM-CSF, IL-1b, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-27, IL-35, osteopontin and stem cell factor (SCF) are upregulated in all or in distinct AML patient groups compared to age-matched controls (39)(40)(41)(42)(43). In contrast to most cytokines, TRAIL and TGF-b levels are decreased in the serum of AML patients (39,43,44). To gain insights into the specific functions of individual cytokines and growth factors in AML, numerous studies have characterized the effects of recombinant cytokines and HGFs on proliferation and colony formation of primary AML cells and cell lines in vitro, thereby establishing ex vivo AML cell culture conditions (see Table 1).…”

“…Osteopontin Elevated PB and BM levels(44, 82, 83) Matrix glycoprotein with proinflammatory cytokine properties Supports AML cell self-renewal, proliferation and survival (84)…”

Macrophage migration inhibitory factor in the pathogenesis of leukemia (Review)

“…AML is a heterogeneous group of diseases characterized by myeloid progenitor cells with abnormal proliferation and differentiation (96). Similar to CLL, the serum levels of MIF are increased in AML compared with healthy bodies (97). This indicates that the presence of MIF in the microenvironment may serve an important role in the pathogenesis of AML.…”