Restored expression of vitamin D receptor and sensitivity to 1,25-dihydroxyvitamin D3 in response to disrupted fusion FOP2–FGFR1 gene in acute myeloid leukemia cells

Marchwicka, Aleksandra; Corcoran, Aoife; Berkowska, Klaudia; Marcinkowska, Ewa

doi:10.1186/s13578-016-0075-9

Cited by 11 publications

(15 citation statements)

References 40 publications

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“…For these malignancies, the mechanism behind this resistance has been studied in an effort to perturb this pathway and restore calcitriol sensitivity. KG1, an AML cell line, is resistant to the differentiating effects of calcitriol contrary to numerous observations of calcitriol sensitivity in other AML cell lines (61,62). This cell line exhibited very low VDR gene expression due to degradation of VDR mRNA (61).…”

Section: Resistance To Calcitriol Treatmentmentioning

confidence: 65%

“…KG1, an AML cell line, is resistant to the differentiating effects of calcitriol contrary to numerous observations of calcitriol sensitivity in other AML cell lines (61,62). This cell line exhibited very low VDR gene expression due to degradation of VDR mRNA (61). Additionally, KG1 had constitutively active STAT1 and increased levels of interferon-stimulated genes resulting from a constitutively active fusion protein FOP2-FGR1 (61).…”

Section: Resistance To Calcitriol Treatmentmentioning

confidence: 81%

“…KG1 exhibited restored sensitivity to calcitriol when FOP2‐FGR1 was disrupted . VDR expression increased after FOP2‐FGR1 was disrupted .…”

Section: Vitamin D Effects On Malignant Hematological Cellsmentioning

confidence: 99%

“…Dysregulation of the Janus kinase (JAK)‐signal transducers and activators of transcription (STAT) pathway is common in leukemias and lymphomas including large granular lymphocytic leukemia (LGLL) , T cell lymphomas , AML , B‐CLL , and T cell acute lymphoblastic leukemia . This aberrant activation can be due to an increase in JAK‐STAT‐promoting cytokines, repression of JAK‐STAT inhibitors, activating mutations in the JAKs or STATs themselves , or fusion proteins as observed in KG1 .…”

Section: Vitamin D Effects On Malignant Hematological Cellsmentioning

confidence: 99%

“…KG1 exhibited restored sensitivity to calcitriol when FOP2-FGR1 was disrupted (61). VDR expression increased after FOP2-FGR1 was disrupted (61). Inhibition of the JAK-STAT signaling pathway leads to apoptosis of several cancer cells, including LGLL (64).…”

Section: Resistance To Calcitriol Treatmentmentioning

confidence: 99%

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Vitamin D in hematological disorders and malignancies

Kulling

Olson

et al. 2016

European J of Haematology

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Commonly known for its critical role in calcium homeostasis and bone mineralization, more recently vitamin D has been implicated in hematological cancer pathogenesis and shows promise as an anti-cancer therapy. Serum levels of 25(OH)D 3 , the precursor to the active form of vitamin D, calcitriol, are frequently lower in patients with hematological disease compared to healthy individuals. This often correlates with worse disease outcome. Furthermore, diseased cells typically highly express the vitamin D receptor, which is required for many of the anti-cancer effects observed in multiple in vivo and in vitro cancer models. In abnormal hematological cells, vitamin D supplementation promotes apoptosis, induces differentiation, inhibits proliferation, sensitizes tumor cells to other anti-cancer therapies, and reduces the production of pro-inflammatory cytokines. Although the dosage of vitamin D required to achieve these effects may induce hypercalcemia in humans, analogs and combinatorial treatments have been developed to circumvent this side effect. Vitamin D and its analogs are well tolerated in clinical trials, and thus, further investigation into the use of these agents in the clinic is warranted. Here, we review the current literature in this field.

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Section: Resistance To Calcitriol Treatmentmentioning

confidence: 65%

Section: Resistance To Calcitriol Treatmentmentioning

confidence: 81%

“…KG1 exhibited restored sensitivity to calcitriol when FOP2‐FGR1 was disrupted . VDR expression increased after FOP2‐FGR1 was disrupted .…”

Section: Vitamin D Effects On Malignant Hematological Cellsmentioning

confidence: 99%

Section: Vitamin D Effects On Malignant Hematological Cellsmentioning

confidence: 99%

Section: Resistance To Calcitriol Treatmentmentioning

confidence: 99%

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Vitamin D in hematological disorders and malignancies

Kulling

Olson

et al. 2016

European J of Haematology

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FGFR families: biological functions and therapeutic interventions in tumors

Liu,

Huang,

Yan

et al. 2023

MedComm

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There are five fibroblast growth factor receptors (FGFRs), namely, FGFR1–FGFR5. When FGFR binds to its ligand, namely, fibroblast growth factor (FGF), it dimerizes and autophosphorylates, thereby activating several key downstream pathways that play an important role in normal physiology, such as the Ras/Raf/mitogen‐activated protein kinase kinase/extracellular signal‐regulated kinase, phosphoinositide 3‐kinase (PI3K)/AKT, phospholipase C gamma/diacylglycerol/protein kinase c, and signal transducer and activator of transcription pathways. Furthermore, as an oncogene, FGFR genetic alterations were found in 7.1% of tumors, and these alterations include gene amplification, gene mutations, gene fusions or rearrangements. Therefore, FGFR amplification, mutations, rearrangements, or fusions are considered as potential biomarkers of FGFR therapeutic response for tyrosine kinase inhibitors (TKIs). However, it is worth noting that with increased use, resistance to TKIs inevitably develops, such as the well‐known gatekeeper mutations. Thus, overcoming the development of drug resistance becomes a serious problem. This review mainly outlines the FGFR family functions, related pathways, and therapeutic agents in tumors with the aim of obtaining better outcomes for cancer patients with FGFR changes. The information provided in this review may provide additional therapeutic ideas for tumor patients with FGFR abnormalities.

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