Protection of the hematopoietic system against radiation-induced damage: drugs, mechanisms, and developments

Wei, Yuanyun; Gong, Yaqi; Wei, Shuang; Chen, Yonglin; Cui, Jian; Lin, Xiang; Yu, Yueqiu; Yan, Hong-xia; Hui, Qing; Liang, Yi

doi:10.1007/s12272-022-01400-7

Cited by 9 publications

(4 citation statements)

References 130 publications

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“…Bone marrow is one of the most sensitive tissues to radiation. Radiation-induced haematopoietic dysfunction is one of the most common problems during unplanned radiation exposures and also in cancer patients receiving radiotherapy [4]. TBI exceeding 3.5 Gy can induce haematopoietic system injury, including myelosuppression, HSCs injury, and haematopoietic progenitor cells injury [29].…”

Section: Discussionmentioning

confidence: 99%

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FG‐4592 protected haematopoietic system from ionising radiation in mice

Wang,

Cheng,

Zhang

et al. 2024

Immunology

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Ionising radiation exposure can lead to acute haematopoietic radiation syndrome. Despite significant advancements in the field of radioprotection, no drugs with high efficacy and low toxicity have yet been approved by the Food and Drug Administration. FG‐4592, as a proline hydroxylase inhibitor, may play an important role in radioprotection of the haematopoietic system. Mice were peritoneal injected with FG‐4592 or normal saline. After irradiation, the survival time, body weight, peripheral blood cell and bone marrow cell (BMC) count, cell apoptosis, pathology were analysed and RNA‐sequence technique (RNA‐Seq) was conducted to explore the mechanism of FG‐4592 in the haematopoietic system. Our results indicated that FG‐4592 improved the survival rate and weight of irradiated mice and protected the spleen, thymus and bone marrow from IR‐induced injury. The number of BMCs was increased and protected against IR‐induced apoptosis. FG‐4592 also promoted the recovery of the blood system and erythroid differentiation. The results of RNA‐Seq and Western blot showed that the NF‐κB signalling pathway and hypoxia‐inducible factor‐1 (HIF‐1) signalling pathway were upregulated by FG‐4592. Meanwhile, RT‐PCR results showed that FG‐4592 could promote inflammatory response significantly. FG‐4592 exhibited radioprotective effects in the haematopoietic system by promoting inflammatory response and targeting the NF‐κB, HIF signalling pathway.

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Section: Discussionmentioning

confidence: 99%

“…Despite the benefits, radiotherapy also induces damage in normal tissues. For example, ionising radiation is very harmful to the haematopoietic system, which is one of the most radiosensitive systems [4]. When the body is irradiated at a dose of 1-7 Gy, it will cause haematopoietic system damage [5].…”

Section: Introductionmentioning

confidence: 99%

FG‐4592 protected haematopoietic system from ionising radiation in mice

Wang,

Cheng,

Zhang

et al. 2024

Immunology

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“…1 After exposure to high dose (>500 mSv) of ionizing radiation (IR), the human body exhibits a series of pathological changes, the most obvious of which are neutropenia and lymphopenia. 2 Ultimately, these may lead to infections, hemorthage, and even death. 3 Bone marrow (BM) is one of the most sensitive organs in the body where hematopoietic stem cells (HSCs) reside in.…”

Section: Introductionmentioning

confidence: 99%

“…Radiation injury usually happens in military, medical, and public health fields 1 . After exposure to high dose (>500 mSv) of ionizing radiation (IR), the human body exhibits a series of pathological changes, the most obvious of which are neutropenia and lymphopenia 2 . Ultimately, these may lead to infections, hemorthage, and even death 3 .…”

Section: Introductionmentioning

confidence: 99%

Near-Infrared Dye Ir-780 Alleviates Hematopoietic System Damage by Promoting Hematopoietic Stem Cells Into Quiescence

Wu,

Ma,

Gong

et al. 2024

Shock

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Worrying about potential radiation exposure is a general concern, but no effective pre-exposure radioprotective countermeasure is generally accepted1. Here, we found a small molecular near-infrared (NIR) dye IR-780, which promoted hematopoietic stem cells (HSCs) into quiescence to resist stress. When mice were treated with IR-780 before stress, increased HSC quiescence and better hematopoietic recovery were observed in IR-780-treated mice in stress conditions. However, when given after radiation, IR-780 did not show obvious benefit. Transplantation assay and colony-forming assay were carried out to determine self-renewal ability and repopulation capacity. Furthermore, IR-780 reduced the generation of reactive oxygen species (ROS) and DNA damage in HSCs after radiation. In homeostasis, the percentage of Lineage-, Sca-1+, and c-Kit+ cells (LSKs) and long-term HSCs (LT-HSCs) were improved, and more HSCs were in G0 state after administration of IR-780. Further investigations showed that IR-780 selectively accumulated in LT-HSCs with high mitochondria membrane potential (MMP) and entered cells by organic anion transporting polypeptides 1b2(Oatp1b2). Finally, IR-780 promoted human CD34+ hematopoietic stem cell reconstruction ability in NOD-PrkdcscidIl2rgnull (NSG) mice after transplantation and improved repopulation capacity in vitro culture. Our research showed that IR-780 selectively entered MMP-high LT-HSCs and promoted them into dormancy, thus reducing hematopoietic injury and improving regeneration capacity. This novel approach might hold promise as a potential radiation countermeasure.

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RNA modification in normal hematopoiesis and hematologic malignancies

Chen,

Yuan,

Zhou

et al. 2024

MedComm

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N6‐methyladenosine (m6A) is the most abundant RNA modification in eukaryotic cells. Previous studies have shown that m6A plays a critical role under both normal physiological and pathological conditions. Hematopoiesis and differentiation are highly regulated processes, and recent studies on m6A mRNA methylation have revealed how this modification controls cell fate in both normal and malignant hematopoietic states. However, despite these insights, a comprehensive understanding of its complex roles between normal hematopoietic development and malignant hematopoietic diseases remains elusive. This review first provides an overview of the components and biological functions of m6A modification regulators. Additionally, it highlights the origin, differentiation process, biological characteristics, and regulatory mechanisms of hematopoietic stem cells, as well as the features, immune properties, and self‐renewal pathways of leukemia stem cells. Last, the article systematically reviews the latest research advancements on the roles and mechanisms of m6A regulatory factors in normal hematopoiesis and related malignant diseases. More importantly, this review explores how targeting m6A regulators and various signaling pathways could effectively intervene in the development of leukemia, providing new insights and potential therapeutic targets. Targeting m6A modification may hold promise for achieving more precise and effective leukemia treatments.

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Protection of the hematopoietic system against radiation-induced damage: drugs, mechanisms, and developments

Cited by 9 publications

References 130 publications

FG‐4592 protected haematopoietic system from ionising radiation in mice

FG‐4592 protected haematopoietic system from ionising radiation in mice

Near-Infrared Dye Ir-780 Alleviates Hematopoietic System Damage by Promoting Hematopoietic Stem Cells Into Quiescence

RNA modification in normal hematopoiesis and hematologic malignancies

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