The Possible Diagnostic and Prognostic Use of Systemic Chemokine Profiles in Clinical Medicine—The Experience in Acute Myeloid Leukemia from Disease Development and Diagnosis via Conventional Chemotherapy to Allogeneic Stem Cell Transplantation

Abstract

Chemokines are important regulators of many different biological processes, including (i) inflammation with activation and local recruitment of immunocompetent cells; (ii) angiogenesis as a part of inflammation or carcinogenesis; and (iii) as a bridge between the coagulation system and inflammation/immune activation. The systemic levels of various chemokines may therefore reflect local disease processes, and such variations may thereby be used in the routine clinical handling of patients. The experience from patients with myeloproliferative diseases, and especially patients with acute myeloid leukemia (AML), suggests that systemic plasma/serum cytokine profiles can be useful, both as a diagnostic tool and for prognostication of patients. However, cytokines/chemokines are released by a wide range of cells and are involved in a wide range of biological processes; the altered levels may therefore mainly reflect the strength and nature of the biological processes, and the optimal clinical use of chemokine/cytokine analyses may therefore require combination with organ-specific biomarkers. Chemokine levels are also altered by clinical procedures, therapeutic interventions and the general status of the patients. A careful standardization of sample collection is therefore important, and the interpretation of the observations will require that the overall clinical context is considered. Despite these limitations, we conclude that analysis of systemic chemokine/cytokine profiles can reflect important clinical characteristics and, therefore, is an important scientific tool that can be used as a part of future clinical studies to identify clinically relevant biomarkers.

Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia

“…There was no significant difference in serum CXCL4 or CXCL7 levels between responders and nonresponders. In addition, we found no significant correlation between BM mRNA levels and serum protein levels for these 2 chemokines, indicating that serum levels of these chemokines are not reflective of mRNA expression in the BM and mirroring previous observations documented for other chemokines in the BM and serum of AML patients (63,64).…”

Cytokine Release Patterns in Mixed Lymphocyte Culture (MLC) of T-Cells with Dendritic Cells (DC) Generated from AML Blasts Contribute to Predict anti-Leukaemic T-Cell Reactions and Patients’ Response to Immunotherapy

“…The attempt to identify particular cytokine patterns in regard to the clinical context might be important since cytokine levels can be influenced by several clinical interventions such as chemotherapy, transfusions etc. and infections (Reikvam et al 2013). However, in our study cytokine concentrations in samples of pts with/without infections did not differ significantly.…”

“…Several studies have shown, that increased levels of IL-6 and TNF-a were observed in pts with untreated AML which decreased with disease control and clinical remission (Reikvam et al 2013). Thus, cytokine levels may act as markers for successful treatment.…”

“…For example it was observed that elevated levels of IL-2, IL4 and IL-10 and decreased levels of TNF-a were associated with clinical remission after intensive chemotherapy. High levels of IL-2 pointed to long-time-survival whereas high serum levels of TNF-a were associated with shorter long-time-survival (Reikvam et al 2013).…”

“…This might indicate that the use of cytokine patterns (potentially together with other mediators such as chemokines, adhesion molecules etc.) may be superior to the use of single cytokines as biomarkers (Reikvam et al 2013).…”