Most cited article - PubMed ID 23223353
The role of cytokines in acute myeloid leukemia: a systematic review
Acute lymphoblastic leukemia (ALL) is the most common childhood hematological malignancy, but it also affects adult patients with worse prognosis and outcomes. Leukemic cells benefit from protective mechanisms, which are mediated by intercellular signaling molecules - cytokines. Through these signals, cytokines modulate the biology of leukemic cells and their surroundings, enhancing the proliferation, survival, and chemoresistance of the disease. This ultimately leads to disease progression, refractoriness, and relapse, decreasing the chances of curability and overall survival of the patients. Targeting and modulating these pathological processes without affecting the healthy physiology is desirable, offering more possibilities for the treatment of ALL patients, which still remains unsatisfactory in certain cases. In this review, we comprehensively analyze the existing literature and ongoing trials regarding the role of chemokines and interleukins in the biology of ALL. Focusing on the functional pathways, genetic background, and critical checkpoints, we constructed a summary of molecules that are promising for prognostic stratification and mainly therapeutic use. Targeted therapy, including chemokine and interleukin pathways, is a new and promising approach to the treatment of cancer. With the expansion of our knowledge, we are able to uncover a spectrum of new potential checkpoints in order to modulate the disease biology. Several cytokine-related targets are advancing toward clinical application, offering the hope of higher disease response rates to treatment.
- Keywords
- Acute lymphoblastic leukemia, Chemokine, Cytokine, Interleukin, Prognostic marker, Targeted therapy,
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma * drug therapy immunology metabolism pathology MeSH
- Chemokines * metabolism immunology MeSH
- Interleukins * metabolism immunology MeSH
- Humans MeSH
- Prognosis MeSH
- Signal Transduction MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Systematic Review MeSH
- Names of Substances
- Chemokines * MeSH
- Interleukins * MeSH
Inflammatory bowel disease (IBD) is a lifelong inflammatory immune mediated disorder, encompassing Crohn's disease (CD) and ulcerative colitis (UC); however, the cause and specific pathogenesis of IBD is yet incompletely understood. Multiple cytokines produced by different immune cell types results in complex functional networks that constitute a highly regulated messaging network of signaling pathways. Applying biological mechanisms underlying IBD at the single omic level, technologies and genetic engineering enable the quantification of the pattern of released cytokines and new insights into the cytokine landscape of IBD. We focus on the existing literature dealing with the biology of pro- or anti-inflammatory cytokines and interactions that facilitate cell-based modulation of the immune system for IBD inflammation. We summarize the main roles of substantial cytokines in IBD related to homeostatic tissue functions and the remodeling of cytokine networks in IBD, which may be specifically valuable for successful cytokine-targeted therapies via marketed products. Cytokines and their receptors are validated targets for multiple therapeutic areas, we review the current strategies for therapeutic intervention and developing cytokine-targeted therapies. New biologics have shown efficacy in the last few decades for the management of IBD; unfortunately, many patients are nonresponsive or develop therapy resistance over time, creating a need for novel therapeutics. Thus, the treatment options for IBD beyond the immune-modifying anti-TNF agents or combination therapies are expanding rapidly. Further studies are needed to fully understand the immune response, networks of cytokines, and the direct pathogenetic relevance regarding individually tailored, safe and efficient targeted-biotherapeutics.
- Keywords
- cytokines, inflammatory bowel disease, novel therapeutic targets,
- Publication type
- Journal Article MeSH
- Review MeSH