Stromal Function in Long Term Bone Marrow Culture of Patients with Acute Myeloid Leukemia

Lisovsky, M; Savchenko, Valeri G.

doi:10.1007/978-3-642-78907-6_93

Cited by 3 publications

(5 citation statements)

References 11 publications

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“…Significant results are shown (*). levels of FL production by human LTBMC or bone marrowderived fibroblasts extent findings by Lisovsky et al 21 who found undetectable production of FL by LTBMC in vitro. The nature of the cells involved in this production remains to be elucidated.…”

Section: Figuresupporting

confidence: 57%

“…IL-1 has also been shown to stimulate FL mRNA expression in bone marrow stromal cells. 21 The IL-1-induced stimulation of FL production may explain the increased capacity of IL-1-stimulated EC to support the proliferation of CFC. 28 We also studied the effect of GC as they are known inhibitors of the production of a large number of hematopoietic growth factors.…”

Section: Figurementioning

confidence: 99%

“…[17][18][19] FL mRNA is expressed by a wide variety of hematopoietic and non-hematopoietic cells. 20,21 FL can be produced as a membrane-bound molecule and as a soluble form likely to derive from the membrane via a proteolytic event. 18,22 Endothelial cells (EC) have been shown to produce many hematopoietic growth factors and may represent a useful model to study the regulation of their expression.…”

Section: Introductionmentioning

confidence: 99%

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Expression of Flt3-ligand by the endothelial cell

Solanilla¹,

Grosset²,

Lemercier³

et al. 2000

Leukemia

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Flt3-ligand (FL) is a cytokine that is of paramount importance in the proliferation of primitive hematopoietic progenitors. In this study, we show that endothelial cells (EC) produce large amounts of soluble FL and express a membrane-bound form of the molecule. Bone marrow microvascular EC also produce FL, suggesting that EC are an important source of FL in the bone marrow. High concentrations of FL in EC supernatants contrast with its undetectable levels in long-term bone marrow cultures. A single mRNA for FL is detected, suggesting that soluble FL derives from the membrane-bound species by proteolytic release. FL mRNA is stable with a half-life of about 3 h. II-1alpha increases FL mRNA levels and membrane and soluble FL expression. Glucocorticoids, known inhibitors for many hematopoietic growth factors do not down-regulate the expression of FL. On the contrary, GC increase the expression of both species of FL. The neutralization of FL in cocultures EC/ hematopoietic progenitors results in an acceleration of the maturation of the progenitors. IFN-alpha, MIP-1 alpha and TGF-beta stimulate production of membrane-bound and soluble FL. This stimulation is essential to explain their modulatory effect on the generation of clonogenic cells in cocultures EC/hematopoietic progenitors. Leukemia (2000) 14, 153-162.

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Section: Figuresupporting

confidence: 57%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of Flt3-ligand by the endothelial cell

Solanilla¹,

Grosset²,

Lemercier³

et al. 2000

Leukemia

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“…The FLT3LG mRNA is detectable in most tissues 34 – 37 but its levels are highest in T cells. Alternative splicing events are frequent for the FLT3LG mRNA, as attested by RNA sequencing (RNA-seq) data obtained with human naïve CD8 + T cells ( Figure S3A ), but the relative abundance and function of the alternative full-length mRNA transcripts have been studied in less detail in human cells than in mice 35 , 38 , 39 .…”

Section: Resultsmentioning

confidence: 99%

FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice

Momenilandi,

Lévy,

Sobrino

et al. 2024

Cell

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“…FLT3LG can be expressed in a variety of cell types, including stromal bone marrow cells and thymocytes 36 , 37 , activated T lymphocytes 38 , and NK cells 39 . NK cells and other lymphocytes are considered to be important sources of FLT3LG in the TME 39 .…”

Section: Discussionmentioning

confidence: 99%

BCG immunotherapy promotes tumor-derived T-cell activation through the FLT3/FLT3LG pathway in bladder cancer

Zhang,

Yu,

Chang

et al. 2024

J. Cancer

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Bladder instillation therapy is a common treatment for superficial or nonmuscle invasive bladder cancer. After surgery or reresection, chemotherapy drugs (epirubicin) or medications such as Bacillus Calmette-Guérin (BCG) are used for bladder instillation therapy, which can reduce the risk of bladder cancer recurrence and progression. However, the specific mechanism by which BCG stimulates the antitumor response has not been thoroughly elucidated. Additionally, although BCG immunotherapy is effective, it is difficult to predict which patients will have a positive response. In this study, we explored the BCG-induced immune response and found that high levels of Fms-related receptor tyrosine kinase 3 ligand (FLT3LG) were expressed after BCG treatment. This FLT3LG can directly act on CD8 + T cells and promote their proliferation and activation. The use of FLT3 inhibitors can neutralize the antitumor effects of BCG. In vitro experiments showed that FLT3LG can synergize with T-cell receptor activators to promote the activation of tumor-derived T cells. This study partially elucidates the mechanism of CD8 + T-cell activation in BCG immunotherapy and provides a theoretical basis for optimizing BCG instillation therapy in bladder cancer

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Stromal Function in Long Term Bone Marrow Culture of Patients with Acute Myeloid Leukemia

Cited by 3 publications

References 11 publications

Expression of Flt3-ligand by the endothelial cell

Expression of Flt3-ligand by the endothelial cell

FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice

BCG immunotherapy promotes tumor-derived T-cell activation through the FLT3/FLT3LG pathway in bladder cancer

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