Stem cells make leukemia grow again

Bahr, Carsten; Correia, Nádia; Trumpp, Andreas

doi:10.15252/embj.201797773

Cited by 11 publications

(9 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Considering the multiple roles played by CSCs in the biological hallmarks of cancer, a working hypothesis is that GSK3β is centrally involved in the underlying mechanism for sustaining CSC phenotypes. CSCs have been identified in glioblastoma and leukemia where they have undergone extensive studies [218,219]. As summarized in Table 1, an earlier study showed that GSK3β suppresses the differentiation of glioblastoma SCs in association with Bmi1, a polycomb group gene required for the self-renewal of neural stem cells [110].…”

Section: Gsk3β Cancer Stem Cells and The "Stemness" Phenotypementioning

confidence: 99%

Glycogen Synthase Kinase 3β in Cancer Biology and Treatment

Domoto

Uehara

Bolidong

et al. 2020

Cells

View full text Add to dashboard Cite

Glycogen synthase kinase (GSK)3β is a multifunctional serine/threonine protein kinase with more than 100 substrates and interacting molecules. GSK3β is normally active in cells and negative regulation of GSK3β activity via phosphorylation of its serine 9 residue is required for most normal cells to maintain homeostasis. Aberrant expression and activity of GSK3β contributes to the pathogenesis and progression of common recalcitrant diseases such as glucose intolerance, neurodegenerative disorders and cancer. Despite recognized roles against several proto-oncoproteins and mediators of the epithelial–mesenchymal transition, deregulated GSK3β also participates in tumor cell survival, evasion of apoptosis, proliferation and invasion, as well as sustaining cancer stemness and inducing therapy resistance. A therapeutic effect from GSK3β inhibition has been demonstrated in 25 different cancer types. Moreover, there is increasing evidence that GSK3β inhibition protects normal cells and tissues from the harmful effects associated with conventional cancer therapies. Here, we review the evidence supporting aberrant GSK3β as a hallmark property of cancer and highlight the beneficial effects of GSK3β inhibition on normal cells and tissues during cancer therapy. The biological rationale for targeting GSK3β in the treatment of cancer is also discussed at length.

show abstract

Section: Gsk3β Cancer Stem Cells and The "Stemness" Phenotypementioning

confidence: 99%

Glycogen Synthase Kinase 3β in Cancer Biology and Treatment

Domoto

Uehara

Bolidong

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Our recent study has demonstrated that FLT3 mutant AML cells can survive and tolerate lethal FLT3 inhibition despite lacking resistance-conferring mutation [101]. Leukemia stem cells (LSCs) have been implicated in driving drug tolerance and relapse, especially in the context of chemotherapy [102][103][104]. LSCs are defined as dormant subpopulation of cells with self-renewing capacity and resistance to chemotherapy and other anti-proliferative drugs [103].…”

Section: Drug-tolerant Persistersmentioning

confidence: 99%

“…Leukemia stem cells (LSCs) have been implicated in driving drug tolerance and relapse, especially in the context of chemotherapy [102][103][104]. LSCs are defined as dormant subpopulation of cells with self-renewing capacity and resistance to chemotherapy and other anti-proliferative drugs [103]. A recent study assessed LSC, as defined by CD34 + CD38-cells, frequency in 869 AML patients at diagnosis and after achieving complete remission (CR) [105].…”

Section: Drug-tolerant Persistersmentioning

confidence: 99%

“…Although the transcriptional profile and surface marker expression of LSCs have been shown to be similar to hematopoietic stem cells (HSCs), LSCs have a plastic gene expression pattern that allows them to be in a dynamic state between stem-and nonstem-like cells [103,106]. Studies using a variety of cancer models have demonstrated that cancer cells can revert to a stem-like state de novo in response to environmental stimuli [97,106,107].…”

Section: Drug-tolerant Persistersmentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic targeting of FLT3 and associated drug resistance in acute myeloid leukemia

Gebru

Wang

2020

J Hematol Oncol

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a heterogeneous disease caused by several gene mutations and cytogenetic abnormalities affecting differentiation and proliferation of myeloid lineage cells. FLT3 is a receptor tyrosine kinase commonly overexpressed or mutated, and its mutations are associated with poor prognosis in AML. Although aggressive chemotherapy often followed by hematopoietic stem cell transplant is the current standard of care, the recent approval of FLT3-targeted drugs is revolutionizing AML treatment that had remained unchanged since the 1970s. However, despite the dramatic clinical response to targeted agents, such as FLT3 inhibitors, remission is almost invariably short-lived and ensued by relapse and drug resistance. Hence, there is an urgent need to understand the molecular mechanisms driving drug resistance in order to prevent relapse. In this review, we discuss FLT3 as a target and highlight current understanding of FLT3 inhibitor resistance.

show abstract

“…Relapse is the major obstacle for patients with leukemia. LSCs are suggested to be relapse‐relevant subpopulations in the leukemic hierarchy because of their self‐renewal and dormancy features . Eradicating LSCs may lead to a cure for leukemia.…”

Section: Resveratrol and Pterostilbene Target Cscsmentioning

confidence: 99%

Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene

Zhang

Wen

et al. 2017

BioFactors

View full text Add to dashboard Cite

In past decades, increasing evidence regarding cancer stem cells (CSCs) may account for carcinogenesis, tumor drug-resistant, and metastasis. CSCs are even considered as the root causes of tumor recurrence and metastases. Targeting CSCs may provide a new clue to cure cancer. Epidemiological and clinical studies have suggested that intake of dietary natural products may bring health benefits including lowering risk of cancer incidence. In this review, we have particularly focused on targeting signaling pathways of CSCs by natural resveratrol and its dimethylated derivative pterostilbene. © 2017 BioFactors, 44(1):61-68, 2018.

show abstract

Stem cells make leukemia grow again

Cited by 11 publications

References 13 publications

Glycogen Synthase Kinase 3β in Cancer Biology and Treatment

Glycogen Synthase Kinase 3β in Cancer Biology and Treatment

Therapeutic targeting of FLT3 and associated drug resistance in acute myeloid leukemia

Targeting cancer stem cells and signaling pathways by resveratrol and pterostilbene

Contact Info

Product

Resources

About