Vitamin D Control of Hematopoietic Cell Differentiation and Leukemia

Studzinski, George P.; Harrison, Jonathan S.; Wang, Xuening; Sarkar, Surojit; Kalia, Vandana; Danilenko, Michael

doi:10.1002/jcb.25104

Cited by 25 publications

(17 citation statements)

References 167 publications

(191 reference statements)

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“…An alternative approach to improve AML therapy is to combine VDDs, including calcitriol, with other compounds. Numerous preclinical studies, principally in vitro, have shown greater differentiation potency of VDDs combined with diverse compounds, when compared to VDDs as sole agents, and were often associated with cell death [5, 6]. However, to date, most clinical trials of these combinations have not been encouraging [7, 8].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of arabinocytosine (AraC) toxicity to AML cells by a differentiation agent combination

Wang

Harrison

Studzinski

2016

The Journal of Steroid Biochemistry and Molecular Biology

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Arabinocytosine (AraC, also known as Cytarabine) is one of the mainstays of AML therapy, but like other DNA damaging therapeutic agents it is rarely curative by itself. There is an emerging realization that the therapeutic outcomes may be improved by combining AraC with other compounds. Here we report that the addition of a differentiating agent combination immediately following AraC damage to AML blasts, selectively increases the cell kill. The experiments were performed using cultured cells from established cell lines of AML (HL60 and U937). The cells were exposed to 100 nM AraC, a concentration which produced approximately 25–50% cell kill, followed by a combination of 100 nM 1alpha-hydroxyvitamin D2 (1-D2) and 10 uM carnosic acid (CA), which together can serve as a powerful differentiating agent combination for AML cells, but are not toxic alone. AraC-induced cell death, measured by Annexin V/Propidium Iodide, was significantly (p<0.01) increased by the 1-D2/CA combination in both cell lines, but not by 1-D2 or CA alone. The enhancement of cell death occurred by both apoptosis and necrosis, was associated with increased DNA damage and with higher levels of DNA damage response (DDR) activated marker Chk1, but the expression of p27, a cell cycle inhibitor protein, was not enhanced by 1-D2/CA. The principal finding is that a vitamin D analog 1-D2 combined with a plant-derived antioxidant CA can markedly augment the cytotoxic action of AraC, an anti-leukemia therapeutic agent.

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Section: Introductionmentioning

confidence: 99%

Enhancement of arabinocytosine (AraC) toxicity to AML cells by a differentiation agent combination

Wang

Harrison

Studzinski

2016

The Journal of Steroid Biochemistry and Molecular Biology

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“…Numerous studies have found that serum VD concentration was altered in many types of diseases including cancers [8][9][10]. In leukemia, studies found that VD had potency in inducing the differentiation of leukemia cells [2,[17][18][19][20]. High serum levels of VD have been found to benefit the survival of AML patients after chemotherapy [21].…”

Section: Discussionmentioning

confidence: 99%

Alteration of Serum 25(OH) Vitamin D, Vitamin D Binding Protein, and C-reactive Protein Levels in Acute Leukemia Patients

Jiang¹,

Zhang²,

Chen³

et al. 2018

Clin. Lab.

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Background: Acute leukemia is a common hematologic malignancy with poorly differentiated leukocytes. Alteration of circulating vitamin D (VD) and its carrier vitamin D binding protein (VDBP) have been reported in certain types of cancers and may play a role in the course of the disease. Understanding of the status of serum VD and VDBP, as well as the acute phase protein C-reactive protein (CRP) levels in pre-and post-treatment of acute leukemia patients, may be helpful in the management of acute leukemia. Methods: Enzyme linked immunosorbent assay (ELISA), chemiluminescence immunoassay, and immunofluorescent assay were used to analyze the 25(OH) vitamin D (25(OH)D), VDBP, and CRP in the serum of a cohort of leukemia patients. Results: Serum 25(OH)D levels in patients (pre-and post-treatment) were significantly lower than in control subjects. There was no significant difference in 25(OH)D levels between pre-and post-treatment. Serum VDBP level was raised in both pre-and post-treatment of acute leukemia patients, with that of pre-treatment being higher. The average serum VDBP was reduced in post-treatment; however, no significant difference was found. Elevated serum CRP levels in both pre-and post-treatment patient groups have been observed but were reduced significantly after treatment. Results also revealed that serum VDBP levels in acute myeloid leukemia patients were significantly higher than in acute lymphoid leukemia patients, while 25(OH)D levels in acute myeloid leukemia were significantly lower than in acute lymphoid leukemia. No significant difference between the serum CRP levels of acute myeloid leukemia and acute lymphoid leukemia was observed. Conclusions: Serum 25(OH)D, VDBP, and CRP may be used together and could be potential indicators of the disease course of acute leukemia and assist in its management which merits further investigation.

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“…The disorder observed was the appearance of chronic myeloid leukaemia-like cells, splenomegaly, granulocytosis and thrombocytosis and reduced erythropoiesis [35]. In vitro studies have revealed that 1,25D3 and its derivatives influence the progeny of HSCs and have largely focussed on an effect on myelopoiesis [36]. We have known for many years that mouse myeloid leukaemia cells differentiate towards monocytes in response to 1,25D3 ( [37] and see below), and that 1,25D3 drives normal blood monocytes to differentiate into macrophages [38].…”

Section: The Direct Influence Of 125d3 On Stem and Progenitor Cell Dmentioning

confidence: 99%

Vitamin D and Haematopoiesis

Brown

Kutner

Marcinkowska

2020

Curr. Tissue Microenviron. Rep.

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Purpose of Review This review examines the influences of active vitamin D on 'developmental' haematopoiesis and the immune cells produced. Haematopoiesis gives rise to the platelets, erythrocytes and a wide range of immune cell types each of which performs a specific role to protect the organism from a myriad of infectious agents. The newly produced immune cells, for example, monocytes, dendritic cells and T and B lymphocytes, are activated in response to the presence of an infectious agent and differentiate further to perform their roles. Recent Findings Binding of 1α,25-dihydroxyvitamin D 3 , the most active metabolite of vitamin D 3 , to its receptor, the vitamin D receptor, regulates the expression of very many different genes and therefore a mode(s) of action of vitamin D relates to the regulation of expression of cell-specific genes. The haematopoietic cytokines are essential regulators of haematopoiesis and the further maturation and functionality of the immune cell types. We now know that some cytokines also instruct the development of a particular type of blood cell. Summary Vitamin D influences the 'early' development of monocytes and invariant natural killer T cells and the further maturation of some immune cell types. Findings regarding the regulation of gene expression have revealed that there are links between the actions of vitamin D and cytokines. Whilst we do not have as yet an entirely clear picture on this matter, there are benefits to 'health' of the immune system from vitamin D supplementation. Keywords Vitamin D. Haematopoiesis. Immune cells. Haematopoietic cytokines. Vitamin D and health This article is part of the Topical Collection on Vitamin D in Tissue Microenvironment * Geoffrey Brown

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Vitamin D Control of Hematopoietic Cell Differentiation and Leukemia

Cited by 25 publications

References 167 publications

Enhancement of arabinocytosine (AraC) toxicity to AML cells by a differentiation agent combination

Enhancement of arabinocytosine (AraC) toxicity to AML cells by a differentiation agent combination

Alteration of Serum 25(OH) Vitamin D, Vitamin D Binding Protein, and C-reactive Protein Levels in Acute Leukemia Patients

Vitamin D and Haematopoiesis

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