![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
ABSTRACT
Introduction
As a vital mechanism of survival, lymphopoiesis requires the collaboration of different signaling molecules to orchestrate each step of cell development and maturation. The PI3K pathway is considerably involved in the maturation of lymphatic cells and therefore, its dysregulation can immensely affect human well-being and cause some of the most prevalent malignancies. As a result, studies that investigate this pathway could pave the way for a better understanding of the lymphopoiesis mechanisms, the undesired changes that lead to cancer progression, and how to design drugs to solve this issue.
Areas covered
The present review addresses the aforementioned aspects of the PI3K pathway and helps pave the way for future therapeutic approaches. In order to access the articles, databases such as Medicine Medline/PubMed, Scopus, Google Scholar, and Science Direct were utilized. The search formula was established by identifying main keywords including PI3K/Akt/mTOR pathway, Lymphopoiesis, Lymphoid malignancies, and inhibitors.
Expert opinion
The PI3K pathway is crucial for lymphocyte development and differentiation, making it a potential target for therapeutic intervention in lymphoid cancers. Studies are focused on developing PI3K inhibitors to impede the progression of hematologic malignancies, highlighting the pathway’s significance in lymphoma and lymphoid leukemia.
Article highlights
The PI3K pathway is crucial in multiple stages of lymphopoiesis, and its various components have the ability to control the intricate process necessary for the proper growth and specialization of lymphocytes, including B cells, T cells, and NK cells.
Any disruption in this pathway may result in the initiation of malignancy, highlighting the potential of the PI3K pathway as a viable therapeutic target for various forms of lymphoid cancers.
Numerous investigations are presently concentrated on formulating PI3K inhibitors with the potential to hinder the advancement of hematologic malignancies.
The conducted research has resulted in encouraging studies and medical tests aimed at improving the effectiveness of PI3K inhibitors and utilizing them as enhancers for other treatments.
Additional trials of a more advanced nature are necessary in order to acquire clinical approval for assessing the impact of PI3K inhibitors on patients with lymphoid malignancies.
Abbreviations
| ABCG2 | = | ATP-binding cassette sub-family G member 2 |
| AID | = | Activation-induced cytidine deaminase |
| Akt | = | Ak strain transforming |
| ALL | = | Acute lymphocytic leukemia |
| APC | = | Antigen-presenting cell |
| BAFF | = | B‐cell activating factor of the TNF family |
| BAM32 | = | B-cell adaptor molecule of 32 kDa |
| BCAP | = | B cell adaptor for phosphoinositide-3-kinase |
| BCL6 | = | B cell lymphoma 6 |
| BCR | = | B cell receptor |
| BET | = | Bromodomain and extra-terminal domain |
| BTK | = | Bruton’s tyrosine kinase |
| CCND2 | = | Cyclin D2 |
| CD | = | Cluster of differentiation |
| CDK | = | Cyclin-dependent kinase |
| CLL | = | Chronic lymphocytic leukemia |
| CML | = | Chronic myelogenous leukemia |
| CMP | = | Common myeloid progenitor |
| CYLD | = | Lysine 63 deubiquitinase |
| DC | = | Dendritic cell |
| DLBCL | = | Diffuse large B-cell lymphoma |
| E/R | = | ETV6/RUNX1 |
| EBV | = | Epstein-Barr Virus |
| ER | = | Endoplasmic reticulum |
| ERK | = | Extracellular signal-regulated kinases |
| FGF7 | = | Fibroblastic growth factor 7 |
| FOXO | = | Class O of forkhead box transcription factors |
| FDA | = | Food and Drug Administration |
| GMSF | = | Granulocyte-macrophage colony-stimulating factor |
| GPCR | = | G protein-coupled receptor |
| GRP78 | = | Glucose-regulated protein 78 |
| GSK-3 | = | Glycogen synthase kinase 3 |
| GVHD | = | Graft-versus-host disease |
| HES1 | = | Hairy/enhancer of split1 |
| HL | = | Hodgkin lymphoma |
| HLXB9 | = | Homeobox HB9 |
| HRS | = | Hodgkin’s/Reed–Sternberg |
| HSC | = | Hematopoietic stem cell |
| HSF1 | = | Heat shock factor 1 |
| HSP | = | Heat shock protein |
| ICOS | = | Inducible T-cell co-stimulator |
| Ig | = | Immunoglobulin |
| IGF-1 | = | Insulin-like growth factor-1 |
| IFN | = | Interferons |
| IL | = | Interleukin |
| IL-R | = | Interleukin receptor |
| ITK | = | IL-2-inducible T-cell kinase |
| KLF10 | = | Kruppel-like factor 10 |
| MADD | = | MAP-kinase activating death domain |
| MAPK | = | Mitogen-activated protein kinase |
| MDR-1 | = | Multidrug-resistant P-glycoprotein |
| miRNA | = | microRNA |
| MM | = | Multiple myeloma |
| mTORC1 | = | Mammalian target of rapamycin complex 1 |
| mTORC2 | = | Mammalian target of rapamycin complex 2 |
| MZ | = | Marginal zone |
| NEAT1 | = | Nuclear paraspeckle assembly transcript 1), |
| NHL | = | Non-Hodgkin lymphoma |
| NK cell | = | Natural killer cell |
| PARP | = | Poly ADP-ribose polymerase |
| PAX5 | = | Paired box protein 5 |
| PDK1 | = | Phosphoinositide-dependent kinase-1 |
| PH domain | = | Pleckstrin-homology domain |
| PHLPP | = | PH domain leucine-rich repeat protein phosphatase |
| PI3K | = | Phosphoinositide 3-kinases |
| PIP3 | = | Phosphatidylinositol-(3,4,5)-trisphosphate |
| PKB | = | Protein kinase B |
| PLCγ | = | Phospholipase Cγ |
| PP2A | = | Protein phosphatase 2 |
| PTEN | = | Phosphatase and tensin homolog |
| RAG | = | Recombination activating gene |
| RLK | = | Resting lymphocyte kinase |
| SHIP1 | = | SH2-containing inositol phosphatases |
| SLC | = | Surrogate light chain |
| SLL | = | Small lymphocytic lymphoma |
| SP | = | Side population |
| TCR | = | T cell receptor |
| TD | = | Thymus-dependent antigen |
| Th | = | T helper |
| TI-2 | = | Thymus-independent type-2 antigen |
| TKR | = | Tyrosine kinase receptor |
| T-LBL | = | T-cell lymphoblastic lymphoma |
| TLR | = | Toll-like receptor |
| TNF-α | = | Tumor necrosis factor alpha |
| Tregs | = | Regulatory T cells |
| TRIM | = | TCR-interacting molecule |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Acknowledgments
The authors would like to express their gratitude to Shahid Beheshti University of Medical Sciences (Tehran, Iran) for supporting this study.