Autocrine Expression of Platelet-Derived Growth Factor B in B Cell Chronic Lymphocytic Leukemia

Ho, Ching‐Liang; Hsu, Lai-Fa; Phyliky, Robert L.; Li, Chin‐Yang

doi:10.1159/000087886

Cited by 21 publications

(24 citation statements)

References 49 publications

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“…Co-culture of UM CLL B cells and autologous T cells resulted in a marked increase in TNF-a, PDGF-BB and IL-8 secretion. These CK have already been described as CLL B cells survival factors [42][43][44] and are known to be inducers of NF-kB. 26,45,46 Consistent with these findings, we observed that stimulation of UM CLL B cells with increasing concentrations of these CK leads to a transient, dose-dependent activation of NF-kB nuclear translocation.…”

Section: Discussionsupporting

confidence: 90%

IGHV unmutated CLL B cells are more prone to spontaneous apoptosis and subject to environmental prosurvival signals than mutated CLL B cells

et al. 2011

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Tumor cells in chronic lymphocytic leukemia (CLL) are more prone to apoptosis when cultured ex vivo, because they lack prosurvival signals furnished in vivo via B-cell receptor (BCR)-dependent and -independent pathways. This study compared the susceptibility of unmutated (UM) and mutated (M) CLL B cells to spontaneous apoptosis and prosurvival signals. UM CLL B cells showed a significantly higher rate of spontaneous apoptosis than M CLL B cells. Nuclear factor-kB (NF-kB) was rapidly inactivated, and B-cell leukemia/lymphoma 2 (Bcl-2) expression progressively down-regulated in the UM CLL B cells. CD40-Ligand, interleukin-4 and stromal cells significantly improved their viability and partially recovered Bcl-2, but not NF-kB expression. Peripheral blood mononuclear cells also offered protection of UM CLL B cells, and recovered both NF-kB and Bcl-2 expression. T cells, rather than nurse-like cells, were responsible for protecting UM CLL B cells by means of cell-to-cell contact and soluble factors. Despite their more aggressive features, UM CLL B cells are more susceptible to spontaneous apoptosis and depend from environmental prosurvival signals. This vulnerability of UM CLL B cells can be exploited as a selective target of therapeutic interventions.

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Section: Discussionsupporting

confidence: 90%

IGHV unmutated CLL B cells are more prone to spontaneous apoptosis and subject to environmental prosurvival signals than mutated CLL B cells

et al. 2011

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“…Notably, the IC50 for both drugs was 3-4-fold higher than for sorafenib. 36 Another well-described target of sorafenib is the PDGFR. 12 In CLL, PDGF signalling is poorly characterized.…”

Section: Discussionmentioning

confidence: 99%

“…Only one paper describes the simultaneous expression of PDGF and PDGFR beta in CLL, suggesting an autocrine feedback loop. 36 However, these results were based on immunohistochemistry of lymph nodes from CLL patients and few data are available regarding a functional role of PDGF. Recently, PDGF-induced production of VEGF production by stromal cells suggested a more indirect role of PDGF for the pathogenesis of CLL.…”

Section: Discussionmentioning

confidence: 99%

Sorafenib induces cell death in chronic lymphocytic leukemia by translational downregulation of Mcl-1

et al. 2011

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“…Our study predicted that within the PDGF family, the two cell types share a common expression profile for the secretory molecules, PDGFB and VEGFC; as well as for the receptors, MET and FLT3. PDGF regulates clonal proliferation in pre-B cell lines and it has been found to be overexpressed in B-chronic leukemia (83). It has also been reported that both VEGF and PDGF families are involved in neo-angiogenesis in embryos and tumors (84).…”

Section: Cytokine/cytokine Interactionsmentioning

confidence: 99%

Pathway simulations in common oncogenic drivers of leukemic and rhabdomyosarcoma cells: A systems biology approach

et al. 2012

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Abstract. A part of current research has intensively been focused on the proliferation and metabolic processes governing biological systems. Since the advent of high throughput methodologies such as microarrays, the load of genomic data has increased geometrically and along with that the need for computational methods to interpret these data. In the present study, we investigated in vitro the common proliferation and metabolic processes, associated with common oncogenic pathways, as far as gene expression is concerned, between the T-cell acute lymphoblastic leukemia (CCRF-CEM) and the rhabdomyosarcoma (TE-671) cell lines. We present a computational approach, using cDNA microarrays, in order to identify commonalities between diverse biological systems. Our analysis predicted that JAK1, STAT1, PIAS2 and CDK4 are the driving forces in the two cell lines. This type of analysis may lead to the understanding of the common mechanisms that transform physiological cells to malignant, and may reveal a new holistic approach to understanding the dynamics of tumor onset as well as the mechanistics behind oncogenic drivers. IntroductionIt is a fact that tumors can be as diverse as the patients carrying them. Due to these differences, tumors are extremely difficult to cure, as the effects of treatments differ depending on the patient. Previously, Nicolis showed that stem cells are found in different tumor types, suggesting that they can be the etiology of tumor maintenance and growth (1). However, there is evidence that even normal, already differentiated cells can be transformed into tumorigenic ones (1). Perilongo et al also reported a case of a child manifesting five different tumor types simultaneously (2). It may be possible that stem cells originating from the same organism possess similar mutations or alterations, thus giving rise to five different tumor types. Therefore, there is a need for the investigation of common pathways between different tumor types. The discovery of similar or opposite gene expression profiles could lead us to the understanding of a common tumor origin, if such exists.A number of studies have investigated the detection of cancer germ line genes (CGGs) both in pediatric sarcomas (3) and pediatric brain tumors (4). The discovery of global antigens for tumor vaccines could become salvatory for childhood malignancies (3). Other studies have reported the common appearance of antigens in Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) with lymphoblastic lymphoma (5). Rhabdomyosarcoma (RMS) belongs to the PNET family of tumors, which utilize embryonic genes for their progression (6). Acute lymphoblastic leukemia (ALL), which originates from the lymphoblast, also uses embryonic mechanisms for its differentiation and progression.Another point which requires attention is the regulation of genes through transcription factors (TFs). Knowledge of gene regulatory networks is considered to be of crucial importance for understanding diseases such as cancer, and may lead to new therapeutic approaches...

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Autocrine Expression of Platelet-Derived Growth Factor B in B Cell Chronic Lymphocytic Leukemia

Cited by 21 publications

References 49 publications

IGHV unmutated CLL B cells are more prone to spontaneous apoptosis and subject to environmental prosurvival signals than mutated CLL B cells

IGHV unmutated CLL B cells are more prone to spontaneous apoptosis and subject to environmental prosurvival signals than mutated CLL B cells

Sorafenib induces cell death in chronic lymphocytic leukemia by translational downregulation of Mcl-1

Pathway simulations in common oncogenic drivers of leukemic and rhabdomyosarcoma cells: A systems biology approach

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