1α,25-Dihydroxyvitamin D3 induces differentiation of human myeloid leukemia cells

Miyaura, Chisato; Abe, Etsuko; Kuribayashi, Takeo; Tanaka, Hirofumi; Konno, Kunio; Nishii, Yasuho; Suda, Toshio

doi:10.1016/0006-291x(81)91628-4

Cited by 436 publications

(156 citation statements)

References 14 publications

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“…Treatment of leukemic cell lines with physiologic concentrations of 1,25(OH) 2 D induces their differentiation into monocytes; an initial proliferation is followed by growth arrest and terminal differentiation [23][24][25]. Recent studies show that 1,25(OH) 2 D binding to its receptor initiates a complex cascade of intracellular molecular events [26].…”

Section: Discussionmentioning

confidence: 99%

Vitamin D insufficiency in myeloproliferative neoplasms and myelodysplastic syndromes: Clinical correlates and prognostic studies

et al. 2011

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Vitamin D insufficiency is commonly observed in the general population; observational studies have suggested an association with increased risk of cancer development. We examined the clinical and prognostic relevance of low plasma levels of 25-hydroxyvitamin D (25[OH]D) in myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). A total of 409 patients were studied: 247 (60%) with primary myelofibrosis (PMF), 74 (18%) with de novo MDS, 63 (15%) with polycythemia vera (PV), and 25 (6%) with essential thrombocythemia (ET). Plasma 25(OH)D levels were measured by liquid chromatography-tandem mass spectrometry; a level lower than 25 ng/mL indicated vitamin D insufficiency and a level lower than 10 ng/mL indicated severe deficiency. The proportion of patients with 25(OH)D insufficiency was significantly greater in PMF (48%) and PV (43%) when compared with ET (28%) and MDS (28%) (P 5 0.01). Severe 25(OH)D deficiency was significantly more frequent in ET (12%) and PMF (9%), compared with PV (3%) and MDS (1%) (P 5 0.05). There were no significant correlations between 25(OH)D insufficiency, or severe deficiency, and a variety of clinical or laboratory variables in PMF, MDS, or PV. Furthermore, Vitamin D insufficiency did not influence either overall or leukemia-free survival in PMF, MDS, or PV (P > 0.05). We conclude that while hypovitaminosis D is relatively common in MPN and MDS, its clinical relevance for prognosis is limited. Although the roles of vitamin D in calcium and bone homeostasis is well established, recent data point to a broader pleiotropic role in nonskeletal tissues with effects on cell proliferation, differentiation, and apoptosis. Vitamin D receptors and the 1a-hydroxylase enzyme necessary for conversion of 25(OH)D to 1,25(OH) 2 D have been detected in multiple tissues; there, 25(OH)D may be converted to the biologically active metabolite and exert paracrine effects in local tissues without affecting serum vitamin D levels.While several observational studies have suggested an association between lower 25(OH)D levels and certain tumors [3,4], this association is not universal (i.e., does not apply to all tumor types) [5,6] and such preliminary obser-

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Section: Discussionmentioning

confidence: 99%

Vitamin D insufficiency in myeloproliferative neoplasms and myelodysplastic syndromes: Clinical correlates and prognostic studies

et al. 2011

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“…VD 3 induces the monocytic differentiation of HL-60 cells. 21 The effects of the combination of MJ and VD 3 were determined using isobogram equation. 18 The combination index was 0.46, indicating synergism.…”

Section: Effects Of Other Inducers On the Mj-induced Differentiation mentioning

confidence: 99%

Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones

et al. 2004

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Some regulators of plant growth and differentiation have been shown to induce the differentiation of several human myeloid leukemia cells, and might be effective as differentiation inducers to control acute myelogenous leukemia cells. In this study, the growth-inhibiting and differentiation-inducing effects of jasmonates on human myeloid leukemia cells were examined. Several myeloid leukemia cells were cultured with methyl jasmonate (MJ) and its derivatives. Cell differentiation was determined by nitroblue tetrazolium-reducing activity, morphological changes, a-naphthyl acetate esterase activity and expression of differentiation-associated surface antigens. MJ induced both monocytic and granulocytic differentiation of HL-60 cells. MJ activated mitogen-activated protein kinase (MAPK) in the cells before causing myelomonocytic differentiation. MAPK activation was necessary for MJ-induced differentiation, since PD98059, an inhibitor of MAPK kinase, suppressed the differentiation induced by MJ. MJ also induced the differentiation of other human leukemia cell lines. Introduction of a double bond at the 4,5-position greatly enhanced the differentiationinducing activity of MJ. MJ and its derivatives potently induce the differentiation of some myelomonocytic leukemia cells. One novel derivative is a particularly promising therapeutic agent for the treatment of leukemia.

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“…5,6 Other investigators also described the differentiation of HL-60 cells into monocytic form following exposure to vitamin D3. 7,8 These initial studies, demonstrating the multipotential character of HL-60 cells to differentiate along various myeloid directions, were summarized in an early review by one of the original discoverers of this important cell line. 9 A number of studies have analyzed transcript levels in the HL-60 cell system, comparing undifferentiated and differentiated cell forms.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomes reflect the phenotypes of undifferentiated, granulocyte and macrophage forms of HL-60/S4 cells

Welch

Jauch

Langowski

et al. 2017

Nucleus

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To understand the chromatin changes underlying differential gene expression during induced differentiation of human leukemic HL-60/S4 cells, we conducted RNA-Seq analysis on quadruplicate cultures of undifferentiated, granulocytic-and macrophage-differentiated cell forms. More than half of mapped genes exhibited altered transcript levels in the differentiated cell forms. In general, more genes showed increased mRNA levels in the granulocytic form and in the macrophage form, than showed decreased levels. The majority of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in genes that exhibited differential transcript levels after either RA or TPA treatment. Changes in transcript levels for groups of genes with characteristic protein phenotypes, such as genes encoding cytoplasmic granular proteins, nuclear envelope and cytoskeletal proteins, cell adhesion proteins, and proteins involved in the cell cycle and apoptosis illustrate the profound differences among the various cell states. In addition to the transcriptome analyses, companion karyotyping by M-FISH of undifferentiated HL-60/S4 cells revealed a plethora of chromosome alterations, compared with normal human cells. The present mRNA profiling provides important information related to nuclear shape changes (e.g., granulocyte lobulation), deformability of the nuclear envelope and linkage between the nuclear envelope and cytoskeleton during induced myeloid chromatin differentiation.

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1α,25-Dihydroxyvitamin D3 induces differentiation of human myeloid leukemia cells

Cited by 436 publications

References 14 publications

Vitamin D insufficiency in myeloproliferative neoplasms and myelodysplastic syndromes: Clinical correlates and prognostic studies

Vitamin D insufficiency in myeloproliferative neoplasms and myelodysplastic syndromes: Clinical correlates and prognostic studies

Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones

Transcriptomes reflect the phenotypes of undifferentiated, granulocyte and macrophage forms of HL-60/S4 cells

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