Loss of FGFR3 Accelerates Bone Marrow Suppression-Induced Hematopoietic Stem and Progenitor Cell Expansion by Activating FGFR1-ELK1-Cyclin D1 Signaling

Ran, Qiuju; Guo, Chen; Sun, Chun; Liu, Qing; He, Huimin; Zhao, Wenjie; Zhang, Jizhou; Xiao, Yong

doi:10.1016/j.bbmt.2020.09.019

Cited by 2 publications

(2 citation statements)

References 30 publications

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“…In our studies, FGFR3-KO mice which were constructed by CRISPR-Cas9 technology display typical bone abnormity as described previously (Deng et al, 1996). Hematopoietic analysis results showed that FGFR3 is dispensable for the functions of HSCs in steady-state hematopoiesis (Ran et al, 2020). To study the functions of FGFR3 in AML, FGFR3-deficient MA-transduced cells were constructed by an infection of retrovirus.…”

Section: Discussionmentioning

confidence: 94%

Loss of FGFR3 Delays Acute Myeloid Leukemogenesis by Programming Weakly Pathogenic CD117-Positive Leukemia Stem-Like Cells

et al. 2021

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Chemotherapeutic patients with leukemia often relapse and produce drug resistance due to the existence of leukemia stem cells (LSCs). Fibroblast growth factor receptor 3 (FGFR3) signaling mediates the drug resistance of LSCs in chronic myeloid leukemia (CML). However, the function of FGFR3 in acute myeloid leukemia (AML) is less understood. Here, we identified that the loss of FGFR3 reprograms MLL-AF9 (MA)-driven murine AML cells into weakly pathogenic CD117-positive leukemia stem-like cells by activating the FGFR1-ERG signaling pathway. FGFR3 deletion significantly inhibits AML cells engraftment in vivo and extends the survival time of leukemic mice. FGFR3 deletion sharply decreased the expression of chemokines and the prolonged survival time in mice receiving FGFR3-deficient MA cells could be neutralized by overexpression of CCL3. Here we firstly found that FGFR3 had a novel regulatory mechanism for the stemness of LSCs in AML, and provided a promising anti-leukemia approach by interrupting FGFR3.

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Section: Discussionmentioning

confidence: 94%

Loss of FGFR3 Delays Acute Myeloid Leukemogenesis by Programming Weakly Pathogenic CD117-Positive Leukemia Stem-Like Cells

et al. 2021

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“…It has been demonstrated that FoxM1 is essential for quiescence maintenance in HSCs by inducing the expression of Nurr1, which preserves quiescence of HSCs via inducing the expression of p21 and p27. In addition, deletion of FoxO1, FoxO3, and FoxO4 increases cell cycling and apoptosis in quiescent HSCs via alteration of the expression of their target genes, including cyclin G2, cyclin D, p21, and p27 [ 41 , 42 ].…”

Section: Ex Vivo Expansion Of Hscsmentioning

confidence: 99%

New Insights into Hematopoietic Stem Cell Expansion to Stimulate Repopulation of the Adult Blood System for Transplantation

Xuan

Liu

et al. 2022

Life

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Successful engraftment of hematopoietic stem cells (HSCs) and progenitor cells (HSPCs) may be considered as a basis for the repopulation of the blood cells after transplantation in adults. Therefore, in vivo and ex vivo expansion of HSCs holds great promise for clinical applications. In this review, the mechanisms of HSC expansion will be discussed, considering the previous studies and works of literature. This is aimed to identify the signaling pathways that regulate HSC expansion and improve the application of engraftment in disease management. The following aspects will be included: (i) Stimulation of HSCs growth in vivo through gene regulation and cytokines activation; (ii) direct or indirect induction of HSC expansion by regulating signaling pathways; (iii) addition to assisting cells to help in the proliferation of HSCs; (iv) changing of living environment in the HSCs cultures via adjusting components and forms of cultures; (v) enhancement of HSC expansion by incorporating substances, such as extracellular vesicles (EVs), UM171, among others. In this review, recent new findings that provide us with new insights into HSC expansion methods have been summarized. Furthermore, these findings will also provide more possibilities for the development of some novel strategies for expanding and engrafting HSCs applied for treatments of some hematopoietic disorders.

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Loss of FGFR3 Accelerates Bone Marrow Suppression-Induced Hematopoietic Stem and Progenitor Cell Expansion by Activating FGFR1-ELK1-Cyclin D1 Signaling

Cited by 2 publications

References 30 publications

Loss of FGFR3 Delays Acute Myeloid Leukemogenesis by Programming Weakly Pathogenic CD117-Positive Leukemia Stem-Like Cells

Loss of FGFR3 Delays Acute Myeloid Leukemogenesis by Programming Weakly Pathogenic CD117-Positive Leukemia Stem-Like Cells

New Insights into Hematopoietic Stem Cell Expansion to Stimulate Repopulation of the Adult Blood System for Transplantation

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