Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

Lin, Zhiyun; Chen, Bobin; Wu, Ting; Xu, Xiaoping

doi:10.1159/000488385

Cited by 6 publications

(5 citation statements)

References 55 publications

(53 reference statements)

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“…22,23 Therefore, discovering a novel reagent or drug targeting LSCs might hold promise for the clinical treatment of AML. According to former studies, 24,25 Traditional Chinese medicine (TCM) normally demonstrates drug acceptance when applied in the disease therapy. Therefore, we speculated that TCM might play a feasible role in treating the senescence of CD34 + CD38 − LSCs in certain signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 induces senescence of leukemic stem cells by upregulating p16INK4a and downregulating hTERT expression

Tang¹,

Wang²,

Zhou³

et al. 2021

Adv Clin Exp Med

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Background. Leukemic stem cells (LSCs) play an important role in the pathogenesis of leukemia. This research attempted to clarify effects of the telomere system on ginsenoside Rg1-induced senescence of LSCs.Objectives. This research attempted to clarify effects of the telomere system on ginsenoside Rg1-induced senescence of LSCs.Materials and methods. CD34 + CD38 − LSCs were isolated, sorted, and divided into a control group and a Rg1 group (treated with 40 μmol/L Rg1). Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation, and flow cytometry was used to assess the cell cycle of CD34 + CD38 − LSCs. The senescenceassociated β-galactosidase (SA-β-Gal) staining and CFU-Mix assay were conducted to measure senescence of CD34 + CD38 − LSCs. The mRNA transcription and protein expression of p16 INK4a and human telomerase reverse transcriptase (hTERT) were determined using a real-time polymerase chain reaction (RT-PCR) and western blot assay, respectively.Results. The Rg1 treatment significantly attenuated proliferative activity and decreased the proliferative index (PI) of CD34 + CD38 − LSCs compared to those of the control group (p < 0.05). It remarkably increased positive SA-β-Gal staining rate, and suppressed formation of the CFU-Mix of CD34 + CD38 − LSCs compared with those of the control group (p < 0.05). The Rg1 treatment markedly boosted telomere effector, p16 INK4a , in CD34 + CD38 − LSCs compared with that of control group (p < 0.05). Such treatment obviously reduced telomere regulator, hTERT, in CD34 + CD38 − LSCs compared with the control group (p < 0.05).Conclusions. Ginsenoside Rg1-induced senescence of CD34 + CD38 − LSCs through upregulating p16 INK4a and downregulating hTERT expression, both of which are associated with telomere systems. The present study would be beneficial for the treatment of leukemia by providing a promising strategy to induce senescence of CD34 + CD38 − LSCs.

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Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 induces senescence of leukemic stem cells by upregulating p16INK4a and downregulating hTERT expression

Tang¹,

Wang²,

Zhou³

et al. 2021

Adv Clin Exp Med

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“…In DLBCL, the upregulation of Notch-3 in tumor cells under close cell-cell contact with BM-derived stromal cells has been implicated in the development of aggressive lymphoma cells ( 61 ). In turn, such direct interaction between DLBCL cells and stromal cells mediates an increase in B-cell activating factor (BAFF) expression by stromal thus resulting in a decrease of chemotherapy-induced B-cell apoptosis ( 62 , 63 ) ( Table 1 ).…”

Section: Lymphoma Bm Stromal Microenvironmentmentioning

confidence: 99%

Bone Marrow Lymphoid Niche Adaptation to Mature B Cell Neoplasms

Dumontet¹,

Mancini²,

Tarte

2021

Front. Immunol.

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B-cell non-Hodgkin lymphoma (B-NHL) evolution and treatment are complicated by a high prevalence of relapses primarily due to the ability of malignant B cells to interact with tumor-supportive lymph node (LN) and bone marrow (BM) microenvironments. In particular, progressive alterations of BM stromal cells sustain the survival, proliferation, and drug resistance of tumor B cells during diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). The current review describes how the crosstalk between BM stromal cells and lymphoma tumor cells triggers the establishment of the tumor supportive niche. DLBCL, FL, and CLL display distinct patterns of BM involvement, but in each case tumor-infiltrating stromal cells, corresponding to cancer-associated fibroblasts, exhibit specific phenotypic and functional features promoting the recruitment, adhesion, and survival of tumor cells. Tumor cell-derived extracellular vesicles have been recently proposed as playing a central role in triggering initial induction of tumor-supportive niches, notably within the BM. Finally, the disruption of the BM stroma reprogramming emerges as a promising therapeutic option in B-cell lymphomas. Targeting the crosstalk between BM stromal cells and malignant B cells, either through the inhibition of stroma-derived B-cell growth factors or through the mobilization of clonal B cells outside their supportive BM niche, should in particular be further evaluated as a way to avoid relapses by abrogating resistance niches.

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“…The role of the BM stromal cells is also prominent in DLBCL. A recent study reported that co-culture of DLBCL cells with stromal cells leads to highly tumorigenic cells ( Lin et al, 2018 ). The mechanism by which the BM stromal cells could induce DLBCL cell growth may be mediated by secreting IL-6 and in a JAK2/STAT3 dependent manner shown in both in vivo and in vitro systems.…”

Section: Diffuse Large B-cell Lymphoma (Dlbcl) and Bm Microenvironmentmentioning

confidence: 99%

Role of the Bone Marrow Niche in Supporting the Pathogenesis of Lymphoid Malignancies

Jalali

Ansell

2021

Front. Cell Dev. Biol.

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While the bone marrow (BM) microenvironment is the primary location for nurturing the multipotent hematopoietic stem cells and developing the blood cells of either myeloid or lymphoid origin under normal physiological conditions, it could provide a supportive milieu for the proliferation of blood cancer cells. In fact, the multiple and complex direct cell-to-cell or indirect soluble factors-mediated interactions taking place among the BM cells of different origins are shown to play a significant role in tumorigenesis of hematological cancers. In the current review, we focus on lymphoid malignancies and highlight the novel insights surrounding the role of both cellular as well as non-cellular BM compartments in modulating hematopoiesis and promoting growth and proliferation of cancer cells across a variety of aggressive and indolent lymphoid malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and Waldenstrom Macroglobulinemia. We also discuss the mechanisms of potential intervention and discuss their therapeutic impact in clinical settings.

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Highly Tumorigenic Diffuse Large B Cell Lymphoma Cells Are Produced by Coculture with Stromal Cells

Cited by 6 publications

References 55 publications

Ginsenoside Rg1 induces senescence of leukemic stem cells by upregulating p16INK4a and downregulating hTERT expression

Ginsenoside Rg1 induces senescence of leukemic stem cells by upregulating p16INK4a and downregulating hTERT expression

Bone Marrow Lymphoid Niche Adaptation to Mature B Cell Neoplasms

Role of the Bone Marrow Niche in Supporting the Pathogenesis of Lymphoid Malignancies

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