Cell cycle regulation and hematologic malignancies
Abstract. A complex network precisely regulates the cell cycle through the G1, S, G2, and M phases and is the basis for cell division under physiological and pathological conditions. On the one hand, the transition from one phase to another as well as the progression within each phase is driven by t...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Health
2019-08-01
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| Series: | Blood Science |
| Online Access: | http://journals.lww.com/10.1097/BS9.0000000000000009 |
| _version_ | 1818744588297306112 |
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| author | Yun Dai Fengyan Jin Wei Wu Shaji K. Kumar |
| author_facet | Yun Dai Fengyan Jin Wei Wu Shaji K. Kumar |
| author_sort | Yun Dai |
| collection | DOAJ |
| description | Abstract. A complex network precisely regulates the cell cycle through the G1, S, G2, and M phases and is the basis for cell division under physiological and pathological conditions. On the one hand, the transition from one phase to another as well as the progression within each phase is driven by the specific cyclin-dependent kinases (CDKs; e.g., CDK1, CDK2, CDK4, CDK6, and CDK7), together with their exclusive partner cyclins (e.g., cyclin A1, B1, D1–3, and E1). On the other hand, these phases are negatively regulated by endogenous CDK inhibitors such as p16ink4a, p18ink4c, p19ink4d, p21cip1, and p27kip1. In addition, several checkpoints control the commitment of cells to replicate DNA and undergo mitosis, thereby avoiding the passage of genomic errors to daughter cells. CDKs are often constitutively activated in cancer, which is characterized by the uncontrolled proliferation of transformed cells, due to genetic and epigenetic abnormalities in the genes involved in the cell cycle. Moreover, several oncogenes and defective tumor suppressors promote malignant changes by stimulating cell cycle entry and progression or disrupting DNA damage responses, including the cell cycle checkpoints, DNA repair mechanisms, and apoptosis. Thus, genes or proteins related to cell cycle regulation remain the main targets of interest in the treatment of various cancer types, including hematologic malignancies. In this context, advances in the understanding of the cell cycle regulatory machinery provide a basis for the development of novel therapeutic approaches. The present article summarizes the pathways as well as their genetic and epigenetic alterations that regulate the cell cycle; moreover, it discusses the various approved or potential therapeutic targets associated with the cell cycle, focusing on hematologic malignancies. |
| first_indexed | 2024-12-18T02:46:41Z |
| format | Article |
| id | doaj.art-ea4d931420e543338cdf30d77616cf2e |
| institution | Directory Open Access Journal |
| issn | 2543-6368 |
| language | English |
| last_indexed | 2024-12-18T02:46:41Z |
| publishDate | 2019-08-01 |
| publisher | Wolters Kluwer Health |
| record_format | Article |
| series | Blood Science |
| spelling | doaj.art-ea4d931420e543338cdf30d77616cf2e2022-12-21T21:23:32ZengWolters Kluwer HealthBlood Science2543-63682019-08-0111344310.1097/BS9.0000000000000009201908000-00007Cell cycle regulation and hematologic malignanciesYun DaiFengyan JinWei WuShaji K. KumarAbstract. A complex network precisely regulates the cell cycle through the G1, S, G2, and M phases and is the basis for cell division under physiological and pathological conditions. On the one hand, the transition from one phase to another as well as the progression within each phase is driven by the specific cyclin-dependent kinases (CDKs; e.g., CDK1, CDK2, CDK4, CDK6, and CDK7), together with their exclusive partner cyclins (e.g., cyclin A1, B1, D1–3, and E1). On the other hand, these phases are negatively regulated by endogenous CDK inhibitors such as p16ink4a, p18ink4c, p19ink4d, p21cip1, and p27kip1. In addition, several checkpoints control the commitment of cells to replicate DNA and undergo mitosis, thereby avoiding the passage of genomic errors to daughter cells. CDKs are often constitutively activated in cancer, which is characterized by the uncontrolled proliferation of transformed cells, due to genetic and epigenetic abnormalities in the genes involved in the cell cycle. Moreover, several oncogenes and defective tumor suppressors promote malignant changes by stimulating cell cycle entry and progression or disrupting DNA damage responses, including the cell cycle checkpoints, DNA repair mechanisms, and apoptosis. Thus, genes or proteins related to cell cycle regulation remain the main targets of interest in the treatment of various cancer types, including hematologic malignancies. In this context, advances in the understanding of the cell cycle regulatory machinery provide a basis for the development of novel therapeutic approaches. The present article summarizes the pathways as well as their genetic and epigenetic alterations that regulate the cell cycle; moreover, it discusses the various approved or potential therapeutic targets associated with the cell cycle, focusing on hematologic malignancies.http://journals.lww.com/10.1097/BS9.0000000000000009 |
| spellingShingle | Yun Dai Fengyan Jin Wei Wu Shaji K. Kumar Cell cycle regulation and hematologic malignancies Blood Science |
| title | Cell cycle regulation and hematologic malignancies |
| title_full | Cell cycle regulation and hematologic malignancies |
| title_fullStr | Cell cycle regulation and hematologic malignancies |
| title_full_unstemmed | Cell cycle regulation and hematologic malignancies |
| title_short | Cell cycle regulation and hematologic malignancies |
| title_sort | cell cycle regulation and hematologic malignancies |
| url | http://journals.lww.com/10.1097/BS9.0000000000000009 |
| work_keys_str_mv | AT yundai cellcycleregulationandhematologicmalignancies AT fengyanjin cellcycleregulationandhematologicmalignancies AT weiwu cellcycleregulationandhematologicmalignancies AT shajikkumar cellcycleregulationandhematologicmalignancies |