Thioredoxin, produced by stromal cells retrieved from the lymph node microenvironment, rescues chronic lymphocytic leukemia cells from apoptosis in vitro

Bäckman, E.; Bergh, Ann-Charlotte; Lagerdahl, Irena; Rydberg, Björn; Sundström, Christer; Tobin, Gerard; Rosenquist, Richard; Linderholm, Mats; Rosén, Anders

doi:10.3324/haematol.11448

Cited by 31 publications

(16 citation statements)

References 31 publications

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“…We suggest that these studies should include experiments that consider activation and proliferation signals generated by specific antigens alone or antigens exposed on apoptotic cells and bacteria, as well as signaling via CD38 55 and its interaction with CD31, involved in "tethering" apoptotic cells. 56 In addition, antiapoptotic signals in the proliferative environment such as stromal cell-derived thioredoxin, 57 Bcl-2 overexpression, 58 or DAPK1 down-regulation 59 may contribute to a vicious circle.…”

Section: Righv3-21m Subset-2mentioning

confidence: 99%

A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies

Myhrinder

Hellqvist

Sidorova

et al. 2008

Blood

239

230

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Section: Righv3-21m Subset-2mentioning

confidence: 99%

A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies

Myhrinder

Hellqvist

Sidorova

et al. 2008

Blood

239

230

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“…Secreted thioredoxin has been implicated in immune responses [20,21] and in cell survival mechanisms [22,23]. Extracellular thioredoxin has been suggested to have chemotactic activity and to act as chemo-attractant for neutrophils, monocytes and Tcells [24].…”

Section: Subcellular Localisation and Functions Of Thioredoxinmentioning

confidence: 99%

The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells

Bhatia¹,

Karlenius²,

Trapani³

et al. 2013

Carcinogenesis

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“…In lymphoid organs, chronic lymphocytic leukemia (CLL) cells are exposed to survival and activation signals from various stromal and immune cells (1)(2)(3). These signals induce proliferation of the otherwise cell cycle-arrested leukemic cells, in line with elevated expression of NF-kB-related molecules, such as the major canonical pathway signaling subunit p65, a molecule suggested as a predictor of clinical outcome in CLL (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

ILK Induction in Lymphoid Organs by a TNFα–NF-κB–Regulated Pathway Promotes the Development of Chronic Lymphocytic Leukemia

et al. 2016

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The proliferation of chronic lymphocytic leukemia (CLL) cells requires communication with the lymphoid organ microenvironment. Integrin-linked kinase (ILK) is a multifunctional intracellular adaptor protein that transmits extracellular signals to regulate malignant cell motility, metastasis, and cell-cycle progression, but is poorly characterized in hematologic malignancies. In this study, we investigated the role of ILK in the context of CLL and observed high ILK expression in patient samples, particularly in tumor cells harboring prognostic high-risk markers such as unmutated IGHV genes, high Zap70, or CD38 expression, or a signature of recent proliferation. We also found increased numbers of Ki67 (MKI67)-positive cells in regions of enhanced ILK expression in lymph nodes from CLL patients. Using coculture conditions mimicking the proliferative lymph node microenvironment, we detected a parallel induction of ILK and cyclin D1 (CCND1) expression in CLL cells that was dependent on the activation of NF-kB signaling by soluble TNFa. The newly synthesized ILK protein colocalized to centrosomal structures and was required for correct centrosome clustering and mitotic spindle organization. Furthermore, we established a mouse model of CLL in which B-cell-specific genetic ablation of ILK resulted in decelerated leukemia development due to reduced organ infiltration and proliferation of CLL cells. Collectively, our findings describe a TNFa-NF-kB-mediated mechanism by which ILK expression is induced in the lymph node microenvironment and propose that ILK promotes leukemogenesis by enabling CLL cells to cope with centrosomal defects acquired during malignant transformation.

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Thioredoxin, produced by stromal cells retrieved from the lymph node microenvironment, rescues chronic lymphocytic leukemia cells from apoptosis in vitro

Cited by 31 publications

References 31 publications

A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies

A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies

The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells

ILK Induction in Lymphoid Organs by a TNFα–NF-κB–Regulated Pathway Promotes the Development of Chronic Lymphocytic Leukemia

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