Association of interleukin-6 and interleukin-8 with poor prognosis in elderly patients with chronic lymphocytic leukemia

Yoon, Ju‐Yoon; Lafarge, Sandrine; Dawe, David E.; Lakhi, Sunjay; Kumar, Rajat; Morales, Carlos Andrés Collazos; Marshall, Aaron J.; Gibson, Spencer B.; Johnston, James B.

doi:10.3109/10428194.2012.666662

Cited by 44 publications

(29 citation statements)

References 41 publications

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“…From a physical health perspective, older adult women with high pro-inflammatory status present with lower relative muscle strength [30]. A higher level of IL-6 is associated with various medical conditions in older adults, including delirium after non-cardiac surgery [31], colorectal carcinoma [32] and poor prognosis in older adult patients with chronic lymphocytic leukemia [33]. A higher level of IL-6 is also associated with a significantly greater risk of disability [34] and mortality [35] in older adults.…”

Section: Discussionmentioning

confidence: 99%

Effects of Horticultural Therapy on Asian Older Adults: A Randomized Controlled Trial

Kst

Sia

Mkw

et al. 2018

IJERPH

112

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The effect of horticultural therapy (HT) on immune and endocrine biomarkers remains largely unknown. We designed a waitlist-control randomized controlled trial to investigate the effectiveness of HT in improving mental well-being and modulating biomarker levels. A total of 59 older adults was recruited, with 29 randomly assigned to the HT intervention and 30 to the waitlist control group. The participants attended weekly intervention sessions for the first 3 months and monthly sessions for the subsequent 3 months. Biological and psychosocial data were collected. Biomarkers included IL-1β, IL-6, sgp-130, CXCL12/SDF-1α, CCL-5/RANTES, BDNF (brain-derived neurotrophic factor), hs-CRP, cortisol and DHEA (dehydroepiandrosterone). Psychosocial measures examined cognitive functions, depression, anxiety, psychological well-being, social connectedness and satisfaction with life. A significant reduction in plasma IL-6 level (p = 0.02) was observed in the HT intervention group. For the waitlist control group, significant reductions in plasma CXCL12 (SDF-1α) (p = 0.003), CXCL5 (RANTES) (p = 0.05) and BDNF (p = 0.003) were observed. A significant improvement in social connectedness was also observed in the HT group (p = 0.01). Conclusion: HT, in reducing plasma IL-6, may prevent inflammatory disorders and through maintaining plasma CXCL12 (SDF-1α), may maintain hematopoietic support to the brain. HT may be applied in communal gardening to enhance the well-being of older adults.

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Section: Discussionmentioning

confidence: 99%

Effects of Horticultural Therapy on Asian Older Adults: A Randomized Controlled Trial

Kst

Sia

Mkw

et al. 2018

IJERPH

112

View full text Add to dashboard Cite

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“…Although IL-6 was not measured directly in splenic microenvironments, high IL-6 levels, which could originate from sources other than stromal cells, are found in the serum of CLL patients and correlate with more aggressive disease. 37 Immunohistochemistry also detects IL-6 in most CLL lymph nodes. 38 Evidence that CLL cells encounter IL-6 in PCs is suggested by microarray studies that demonstrate increased expression of the IL-6 signature gene IL4RA by recent emigrants to the circulation.…”

Section: Discussionmentioning

confidence: 99%

Microenvironmental interleukin-6 suppresses toll-like receptor signaling in human leukemia cells through miR-17/19A

Shi

McCaw

et al. 2015

Blood

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Key Points• IL-6 from splenic stromal cells prevents CLL cells from responding strongly to TLR ligands.• IL-6-signaling inhibitors enhance TLR-mediated responses of CLL cells in vitro and in vivo.The regulation of toll-like receptor (TLR) signaling in a tumor microenvironment is poorly understood despite its importance in cancer biology. To address this problem, TLR7-responses of chronic lymphocytic leukemia (CLL) cells were studied in the presence and absence of a human stromal cell-line derived from a leukemic spleen. CLL cells alone produced high levels of tumor necrosis factor (TNF)-a and proliferated in response to TLR7-agonists. A signal transducer and activator of transcription 3 -activating stromal factor, identified as interleukin (IL)-6, was found to upregulate microRNA (miR)-17 and miR-19a, target TLR7 and TNFA messenger RNA, and induce a state of tolerance to TLR7-agonists in CLL cells. Overexpression of the miR-17-92 cluster tolerized CLL cells directly and miR-17 and miR-19a antagomiRs restored TLR7-signaling. Inhibition of IL-6 signaling with antibodies or small-molecule Janus kinase inhibitors reversed tolerization and increased TLR7-stimulated CLL cell numbers in vitro and in NOD-SCIDg c null mice. These results suggest IL-6 can act as tumor suppressor in CLL by inhibiting TLR-signaling. (Blood. 2015;126(6):766-778)

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“…Interestingly, IL-6 and IL-8 were upregulated in the LN but both cytokine were not present in the REH-CM itself, suggesting that their secretion by MSC is induced only by soluble factors secreted by the REH cells. Noteworthy, IL-6 and IL-8 levels increased in serum of leukemic patients and correlated with adverse clinical effects and short survival [52, 53]. Consistently with this, IL-6 and IL-8 were also the major secreted cytokines found in a LN set directly with REH cells.…”

Section: Discussionmentioning

confidence: 68%

Loss of quiescence and self-renewal capacity of hematopoietic stem cell in an in vitro leukemic niche

Vanegas

Vernot

2017

Exp Hematol Oncol

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BackgroundLeukemic and mesenchymal stem cells interact in the leukemic microenvironment and affect each other differently. This interplay has also important implications for the hematopoietic stem cell (HSC) biology and function. This study evaluated human HSC self-renewal potential and quiescence in an in vitro leukemic niche without leukemic cells.MethodsA leukemic niche was established by co-culturing mesenchymal stem cells with a fresh conditioned medium obtained from a leukemic (REH) cell line. After 3 days, the REH-conditioned medium was removed and freshly isolated CD34+ at a density of up to 100,000 cells/ml were added to the leukemic niche. CD34+ cell evaluations (cell cycle, self-renewal gene expression and migration capacity) were performed after 3 further days of co-culture. Additionally, we preliminary investigated the soluble factors present in the leukemic niche and their effect on the mesenchymal stem cells. Statistical significance was assessed by Student’s t test or the nonparametric test Kolmogorov–Smirnov.ResultsBy co-culturing normal mesenchymal stem cells with the REH-conditioned medium we showed that hematopoietic stem cells, normally in a quiescent state, enter cell cycle and proliferate. This loss of quiescence was accompanied by an increased expression of Ki-67 and c-Myc, two well-known cell proliferation-associated markers. Two central regulators of quiescence GATA2 and p53 were also down regulated. Importantly, two genes involved in HSC self-renewal, Klf4 and the histone–lysine N-methyltransferase enzyme Ezh2, were severely affected. On the contrary, c-Kit expression, the stem cell factor receptor, was upregulated in hematopoietic stem cells when compared to the normal niche. Interestingly, mesenchymal stem cells incubated with the REH-conditioned medium stopped growing, showed a flattened morphology with the appearance of small vacuoles, and importantly, became positive for the senescence-associated beta-galactosidase activity. Evaluation of the leukemic-conditioned medium showed increased IL-6 and IL-8, suggesting that these cytokines could be responsible for the observed changes.ConclusionsOur results showed that quiescence and self-renewal are severely affected in this leukemic niche. This in vitro leukemic niche, established without leukemic cells, will facilitate HSC gene expression evaluation and the development of therapeutic agents aimed to neutralize soluble factors and the cell signaling pathways involved in HSC alterations.Electronic supplementary materialThe online version of this article (doi:10.1186/s40164-016-0062-1) contains supplementary material, which is available to authorized users.

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Association of interleukin-6 and interleukin-8 with poor prognosis in elderly patients with chronic lymphocytic leukemia

Cited by 44 publications

References 41 publications

Effects of Horticultural Therapy on Asian Older Adults: A Randomized Controlled Trial

Effects of Horticultural Therapy on Asian Older Adults: A Randomized Controlled Trial

Microenvironmental interleukin-6 suppresses toll-like receptor signaling in human leukemia cells through miR-17/19A

Loss of quiescence and self-renewal capacity of hematopoietic stem cell in an in vitro leukemic niche

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