FLI1 accelerates leukemogenesis through transcriptional regulation of pyruvate kinase-L/R and other glycolytic genes

Sheng, Danmei; Chen, Beiling; Wang, Chunlin; Xiao, Xiao; Hu, Anling; Liu, Wuling; Kuang, Yi; Sample, Klarke M.; Zacksenhaus, Eldad; Gajendran, Babu; Pan, Weidong; Ben‐David, Yaacov

doi:10.1007/s12032-022-01867-w

Cited by 5 publications

(3 citation statements)

References 31 publications

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“…FLI1 is the most highly expressed BMF and/or HM TF predisposition gene in both myeloid and lymphoid lineages during most stages of hematopoiesis ( Figure 2 ), and directly regulates expression of various target genes within its broad target gene program, which may be the mechanism behind its BMF association. For example, FLI1s large transcriptional target program allows the protein to alter glycolysis, shifting the glycolytic balance to be more aerobic to enable robust cell division, and through the repression of the PKLR (pyruvate kinase) promoter, can initiate a block in erythroid differentiation ( 210 ). Despite its colocalization with GATA1/2 and RUNX1 ( 211 ), FLI1 has also been shown to cooperate with RUNX1 by co-binding to ETS-RUNX motifs, to restrain transcription factors that aid T-cell differentiation ( 212 ).…”

Section: Biological Mechanisms Of Bmf And/or Hm Predisposition Tfsmentioning

confidence: 99%

Transcription factor genetics and biology in predisposition to bone marrow failure and hematological malignancy

Zerella,

Homan,

Arts

et al. 2023

Front. Oncol.

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Transcription factors (TFs) play a critical role as key mediators of a multitude of developmental pathways, with highly regulated and tightly organized networks crucial for determining both the timing and pattern of tissue development. TFs can act as master regulators of both primitive and definitive hematopoiesis, tightly controlling the behavior of hematopoietic stem and progenitor cells (HSPCs). These networks control the functional regulation of HSPCs including self-renewal, proliferation, and differentiation dynamics, which are essential to normal hematopoiesis. Defining the key players and dynamics of these hematopoietic transcriptional networks is essential to understanding both normal hematopoiesis and how genetic aberrations in TFs and their networks can predispose to hematopoietic disease including bone marrow failure (BMF) and hematological malignancy (HM). Despite their multifaceted and complex involvement in hematological development, advances in genetic screening along with elegant multi-omics and model system studies are shedding light on how hematopoietic TFs interact and network to achieve normal cell fates and their role in disease etiology. This review focuses on TFs which predispose to BMF and HM, identifies potential novel candidate predisposing TF genes, and examines putative biological mechanisms leading to these phenotypes. A better understanding of the genetics and molecular biology of hematopoietic TFs, as well as identifying novel genes and genetic variants predisposing to BMF and HM, will accelerate the development of preventative strategies, improve clinical management and counseling, and help define targeted treatments for these diseases.

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Section: Biological Mechanisms Of Bmf And/or Hm Predisposition Tfsmentioning

confidence: 99%

Transcription factor genetics and biology in predisposition to bone marrow failure and hematological malignancy

Zerella,

Homan,

Arts

et al. 2023

Front. Oncol.

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“…Upregulation of genes involved in glycolysis and concomitant downregulation of tricarboxylic acid genes were observed in B precursor ALL lymphoblasts compared with normal hematopoietic progenitor cells, while inhibition of glycolysis induces the apoptosis of leukemia cells, suggesting a dependence on glycolysis for leukemia cell survival (Boag et al, 2006). The ETSrelated transcriptional factor Fli-1 plays an important role in the induction and progression of leukemia in part by inducing glycolysis (Sheng et al, 2022). As a pyruvate kinase M2 (PKM2) inhibitor, SHK could inhibit the proliferation of HEL leukemia cells through inhibition of glycolysis.…”

Section: Modulation Of Glucose Metabolismmentioning

confidence: 99%

“…As a pyruvate kinase M2 (PKM2) inhibitor, SHK could inhibit the proliferation of HEL leukemia cells through inhibition of glycolysis. Furthermore, downregulation the expression of Fli-1 in a dose-dependent manner by SHK indicating it may suppress glycolysis indirectly (Sheng et al, 2022). C-MYC and GLUT2 are two key regulators of glycolysis, which are targets of Hippo signaling pathway in human Jurkat leukemia cells (Vališ et al, 2016).…”

Section: Modulation Of Glucose Metabolismmentioning

confidence: 99%

The anti-leukemia activity and mechanisms of shikonin: a mini review

Dong,

Chang,

Gao

et al. 2023

Front. Pharmacol.

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Leukemia encompasses a group of highly heterogeneous diseases that pose a serious threat to human health. The long-term outcome of patients with leukemia still needs to be improved and new effective therapeutic strategies continue to be an unmet clinical need. Shikonin (SHK) is a naphthoquinone derivative that shows multiple biological function includes anti-tumor, anti-inflammatory, and anti-allergic effects. Numerous studies have reported the anti-leukemia activity of SHK during the last 3 decades and there are studies showing that SHK is particularly effective towards various leukemia cells compared to solid tumors. In this review, we will discuss the anti-leukemia effect of SHK and summarize the underlying mechanisms. Therefore, SHK may be a promising agent to be developed as an anti-leukemia drug.

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Rocaglamide reprograms glucose metabolism in erythroleukemic cells via c-MYC transcriptional regulation of TXNIP and HK2

Song,

Liu,

Xiao

et al. 2025

Journal of Ethnopharmacology

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FLI1 accelerates leukemogenesis through transcriptional regulation of pyruvate kinase-L/R and other glycolytic genes

Cited by 5 publications

References 31 publications

Transcription factor genetics and biology in predisposition to bone marrow failure and hematological malignancy

Transcription factor genetics and biology in predisposition to bone marrow failure and hematological malignancy

The anti-leukemia activity and mechanisms of shikonin: a mini review

Rocaglamide reprograms glucose metabolism in erythroleukemic cells via c-MYC transcriptional regulation of TXNIP and HK2

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