The role of cytokines in acute myeloid leukemia: A systematic review

Abstract

Background. Acute myeloid leukemia (AML) shows a high degree of heterogeneity owing to a variety of mutations and the mechanisms of leukemogenesis. This heterogeneity is often not reflected in standard treatment approaches which while providing predictable outcomes in the majority of patients fail in particular cases even with high-dose multiagent chemotherapy regimens. Further, the unselective effect of chemotherapy leads to high treatment-related toxicity and the enormous risk of infection during prolonged pancytopenia, preventing further dose escalation. Objectives. Cytokines play a role in leukemogenesis, AML cell persistence and treatment outcome. In this review we highlight cytokine dependent mechanisms essential for AML cell survival and the role of single cytokines in leukemogenesis and allogeneic transplantation-related phenomena. Cytokine-related mechanisms of leukemogenesis, AML cell persistence and resistance to chemotherapy are complex. Modulation of the cytokine network can disrupt signalling pathway activation and overcome the high resistance to treatment. It may also increase the selectivity of AML treatment, reduce the overall treatment-related toxicity and improve outcomes of AML treatment in all age groups of patients. Conclusions. This review provides a deeper insight into these processes with focus on the most vulnerable step. Special attention is paid to the possibility of selective influence on defined cell populations for therapeutic target. We believe that modulating cytokine-dependent processes in AML is an approach that could be included in standard chemotherapeutic regimens for improving overall treatment outcome.

Multi-analytical evaluation of serum levels of cytokines and adhesion molecules in patients treated for acute myeloid leukemia using biochip array technology

“…3,4 ). Alterations in this interacting functional network may have direct effect on the malignant cells or have indirect effect on leukemogenesis through altered functions of bone marrow stromal elements 5,6 .…”

Evaluation of cytokines and soluble adhesion molecules in patients with newly diagnosed acute myeloid leukemia: the role of TNF-alpha and FLT3-ITD

“…15,16 ). An inflammatory environment is asscociated with tumor progression 15 and this shows that tumors are dynamic, interacting systems.…”

Down-Regulation of Mcl-1 by Small Interference RNA Induces Apoptosis and Sensitizes HL-60 Leukemia Cells to Etoposide

“…AML is commonly associated as a disease of the elderly, with the majority of patients dying with the condition. (Kupsa et al, 2012). Standard treatment options for AML are chemotherapy and hematopoietic stem cell transplantation (Robak and Wierzbowska, 2009;Smits et al, 2009).…”

“…The majority of patients with AML does not achieve complete remission (CR) or are expected to relapse even with intensive chemotherapy. This is mainly due to the development of drug resistance in tumor cells (Xiao et al, 2009;Kupsa et al, 2012;Szer, 2012). In addition, owing to the occurrence of relapse and development of graft-versus-host-disease (GVHD) in stem cell transplantation, the treatment of these patients is still controversial (Robak and Wierzbowska, 2009;Smits et al, 2009).…”