Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations

Sabatier, Marie; Boet, Emeline; Zaghdoudi, Sonia; Guiraud, Nathan; Hucteau, Alexis; Polley, Nathaniel; Cognet, Guillaume; Saland, Estelle; Lauture, Laura; Farge, Thomas; Sahal, Ambrine; Pancaldi, Véra; Chu‐Van, Emeline; Castelli, Florence; Bertoli, Sarah; Bories, Pierre; Récher, Christian; Boutzen, Héléna; Mas, Véronique Mansat‐De; Stuani, Lucille; Sarry, Jean-Emmanuel

doi:10.3390/cancers13205243

Cited by 7 publications

(5 citation statements)

References 51 publications

(85 reference statements)

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“…Interestingly, a recent study reports that liganded VDR has a strong prodifferentiation effect in acute myeloid leukemia cells harboring mutations in IDH gene encoding isocitrate dehydrogenase. This is the case because the oncometabolite 2-hydroxyglutarate that is produced by mutant IDH potentiates VDR signaling in a CEBPα-dependent manner [ 205 ]. In addition, prodifferentiation effects of VDR agonists have been reported in follicular non-Hodgkin’s lymphoma cells, with increased expression of mature B-cell markers [ 206 ].…”

Section: Mechanisms Introductionmentioning

confidence: 99%

Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

2022

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This is a narrative review of the evidence supporting vitamin D’s anticancer actions. The first section reviews the findings from ecological studies of cancer with respect to indices of solar radiation, which found a reduced risk of incidence and mortality for approximately 23 types of cancer. Meta-analyses of observational studies reported the inverse correlations of serum 25-hydroxyvitamin D [25(OH)D] with the incidence of 12 types of cancer. Case-control studies with a 25(OH)D concentration measured near the time of cancer diagnosis are stronger than nested case-control and cohort studies as long follow-up times reduce the correlations due to changes in 25(OH)D with time. There is no evidence that undiagnosed cancer reduces 25(OH)D concentrations unless the cancer is at a very advanced stage. Meta-analyses of cancer incidence with respect to dietary intake have had limited success due to the low amount of vitamin D in most diets. An analysis of 25(OH)D-cancer incidence rates suggests that achieving 80 ng/mL vs. 10 ng/mL would reduce cancer incidence rates by 70 ± 10%. Clinical trials have provided limited support for the UVB-vitamin D-cancer hypothesis due to poor design and execution. In recent decades, many experimental studies in cultured cells and animal models have described a wide range of anticancer effects of vitamin D compounds. This paper will review studies showing the inhibition of tumor cell proliferation, dedifferentiation, and invasion together with the sensitization to proapoptotic agents. Moreover, 1,25-(OH)2D3 and other vitamin D receptor agonists modulate the biology of several types of stromal cells such as fibroblasts, endothelial and immune cells in a way that interferes the apparition of metastases. In sum, the available mechanistic data support the global protective action of vitamin D against several important types of cancer.

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Section: Mechanisms Introductionmentioning

confidence: 99%

Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

2022

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“…Through in vitro studies with different cell lines, multiple pathways and signals are proof related to AML cell differentiation and can be affected by VDR [ 123 , 124 ]. These were also proofed in some in vivo studies with mice and further confirmed the possibility of increasing survival within mice [ 125 , 126 , 127 , 128 , 129 ]. Regarding clinical experience, there was no inspiring development in this field.…”

Section: Application Of Natural Products In Aml Therapymentioning

confidence: 54%

Targeting the Tumor Microenvironment in Acute Myeloid Leukemia: The Future of Immunotherapy and Natural Products

et al. 2022

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The tumor microenvironment (TME) plays an essential role in the development, proliferation, and survival of leukemic blasts in acute myeloid leukemia (AML). Within the bone marrow and peripheral blood, various phenotypically and functionally altered cells in the TME provide critical signals to suppress the anti-tumor immune response, allowing tumor cells to evade elimination. Thus, unraveling the complex interplay between AML and its microenvironment may have important clinical implications and are essential to directing the development of novel targeted therapies. This review summarizes recent advancements in our understanding of the AML TME and its ramifications on current immunotherapeutic strategies. We further review the role of natural products in modulating the TME to enhance response to immunotherapy.

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“…AML cells with IDH-R132H mutation also have higher levels of VDR and RXRα proteins than the cells with wt-IDH. Consequently, these cells respond better to 1,25D than wt-IDH cells, and even better to the combination of 1,25D and ATRA [ 84 ].…”

Section: Amls Sensitive To 125dmentioning

confidence: 99%

Vitamin D Derivatives in Acute Myeloid Leukemia: The Matter of Selecting the Right Targets

Marcinkowska

2022

Nutrients

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Acute myeloid leukemia (AML) is an aggressive and often fatal hematopoietic malignancy. A very attractive way to treat myeloid leukemia, called “differentiation therapy”, was proposed when in vitro studies showed that some compounds are capable of inducing differentiation of AML cell lines. One of the differentiation-inducing agents, all-trans-retinoic acid (ATRA), which can induce granulocytic differentiation in AML cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a chromosomal translocation. ATRA has greatly improved the treatment of APL. Since 1,25-dihydroxyvitamin D (1,25D) is capable of inducing monocytic differentiation of leukemic cells, the idea of treating other AMLs with vitamin D analogs was widely accepted. However, early clinical trials in which cancer patients were treated either with 1,25D or with analogs did not lead to conclusive results. Recent results have shown that AML types with certain mutations, such as isocitrate dehydrogenase (IDH) mutations, may be the right targets for differentiation therapy using 1,25D, due to upregulation of vitamin D receptor (VDR) pathway.

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Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations

Cited by 7 publications

References 51 publications

Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

Vitamin D and Cancer: An Historical Overview of the Epidemiology and Mechanisms

Targeting the Tumor Microenvironment in Acute Myeloid Leukemia: The Future of Immunotherapy and Natural Products

Vitamin D Derivatives in Acute Myeloid Leukemia: The Matter of Selecting the Right Targets

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