Leukemic cells and the cytokine patchwork

Kiss, Csongor; Benkö, Ilona; Kovács, P.

doi:10.1002/pbc.10436

Cited by 14 publications

(15 citation statements)

References 98 publications

(128 reference statements)

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“…In particular, γ interleukins were reported to have proliferative and differentiating effects on T-ALL primary cells (77). Despite the differences between normal blood stem cells and malignant ones, they both use cytokine signaling for progression and differentiation (78). Our analysis predicted IL8, IL9 and the IL2 receptor.…”

Section: Cytokine/cytokine Interactionsmentioning

confidence: 96%

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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Section: Cytokine/cytokine Interactionsmentioning

confidence: 96%

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

et al. 2012

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“…Aguayo et al (23) have shown that VEGF-A and related growth factors enhance the bone marrow microvasculature in bone marrow biopsies in relapsed leukemia patients. Quiescent residual leukemia stem cells may also be stimulated into cell replication by VEGF-A and other growth factors (2,4,5,9,12,15,23,24,31,39,40).…”

Section: Discussionmentioning

confidence: 99%

“…This phenomenon seemed to correlate with cellular drug resistance to anthracyclines. In leukemia, the clonal population is characterized by a hierarchical organization similar to the normal hematopoiesis and a subset of the stem cells retain their undifferentiated ''stem cell'' morphology (2). The cytokine effect on acute lymphoblastic leukemia (ALL) stem cells, especially childhood T-cell ALL cells, seems to be similar to normal hematopoietic bone marrow cells.…”

mentioning

confidence: 99%

Correlation between High Vascular Endothelial Growth Factor-A Serum Levels and Treatment Outcome in Patients with Standard-Risk Acute Lymphoblastic Leukemia: A Report from Children's Oncology Group Study CCG-1962

Avramis

Panosyan

Dorey

et al. 2006

Clinical Cancer Research

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Purpose: Many molecular pathways, including cell cycle control, angiogenesis, and drug resistance, mediate tumor growth and survival. Vascular endothelial growth factor-A (VEGF-A) serum levels <40 and >100 pg/mL have been associated with good and poor prognoses, respectively. Experimental Design: The hypothesis was that serum VEGF-A levels in standard-risk acute lymphoblastic leukemia pediatric patients at induction are predictive of event-free survival (EFS). One hundred seventeen patients were entered in CCG-1962 study and randomized into the native and polyethylene glycolated asparaginase arms. VEGF-A levels were quantified by an ELISA assay. Results: All patients had a decrease in VEGF-A levels by day 14 of induction, but they later dichotomized; EFS group levels remained low and event group levels increased. A correlation exists between high VEGF-A levels at entry to induction and time to event. Moreover, 6-year EFS patients have lower end of induction VEGF-A levels (28 ± 6 pg/mL) than event patients (>100 pg/mL; P < 0.01). Kaplan-Meier curves using various VEGF-A values were produced; with ≤30 at entry into induction (day 0) and ≤60 pg/mL at the end of induction (day 28), patients with low VEGF-A levels had superior EFS (P < 1e−4). Furthermore, patients who had an increase in VEGF-A during induction (ΔVEGF-positive, days 0-28) were more likely to have an event (P < 1e−4). Bifurcation by asparaginase treatment arm did not alter these results. Conclusions: These observations strongly support that high VEGF-A levels in induction are an asparaginase treatment–independent predictive marker for EFS. Hence, an anti-VEGF-A therapy should be tested in acute lymphoblastic leukemia.

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“…One of the genetic factors may be an aberration of cytokine regulation and cytokine production, which can lead to an increased apoptosis of hematopoietic progenitor cells, and aberrant hematopoiesis. The excessive production of growth-inhibitory cytokines such as TNF-␣ in patients with MDS has been described [3,4,29] . Recent data indicate that TGF-␤ inhibits myeloid, erythroid, megakaryocytic and multilineage colony formation [5][6][7] .…”

Section: Discussionmentioning

confidence: 99%

“…A number of investigators have demonstrated an excessive production of proapoptotic cytokines in the bone marrow of MDS patients. Several studies have stressed the im portance of increased levels of tumor necrosis factor-␣ (TNF-␣ ) in the serum and bone marrow in promoting apoptosis [3,4] . Transforming growth factor-␤ (TGF-␤ ) is another cytokine which is generally considered to be a negative key regulator of hematopoietic stem and progenitor cells [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Clinical Importance of Transforming Growth Factor-β but Not of Tumor Necrosis Factor-α Gene Polymorphisms in Patients with the Myelodysplastic Syndrome Belonging to the Refractory Anemia Subtype

et al. 2005

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Objectives: Tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) are cytokines that play key roles in the myelodysplastic syndrome (MDS). There have been several reports on the presence of genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-β1 protein, located in codon 10 in exon 1 and in the –308 promoter region of TNF-α. The objective of this study was to investigate the association between TNF-α and TGF-β1 gene polymorphisms and the susceptibility to MDS and the progression of the disease among patients with MDS belonging to the refractory anemia (RA) subtype. Methods: The diagnosis of MDS (n = 50) was based on the FAB criteria. The TNF-α genotypes were analyzed by PCR-RFLP and the TGF-β genotypes were analyzed using an amplification refractory mutation system. Results and Conclusions: Compared with healthy control subjects, patients with RA showed no significant deviations in genotype or allele frequencies of TNF-α. The TT homozygosity at codon 10 of TGF-β1 was significantly higher among patients with bi- or pancytopenia (severe group) than in the patients with anemia only (mild group; odds ratio = 6.99, p = 0.003). These findings suggest that the TGF-β1 gene polymorphism in codon 10 and the –308 TNF-α gene polymorphism do not predispose to the development of RA, but the TGF-β1 gene polymorphism may affect disease progression.

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Leukemic cells and the cytokine patchwork

Cited by 14 publications

References 98 publications

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

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

Correlation between High Vascular Endothelial Growth Factor-A Serum Levels and Treatment Outcome in Patients with Standard-Risk Acute Lymphoblastic Leukemia: A Report from Children's Oncology Group Study CCG-1962

Clinical Importance of Transforming Growth Factor-β but Not of Tumor Necrosis Factor-α Gene Polymorphisms in Patients with the Myelodysplastic Syndrome Belonging to the Refractory Anemia Subtype

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