Gene expression profiles of Hodgkin's lymphoma cell lines with different sensitivity to cytotoxic drugs

Staege, Martin S.; Banning-Eichenseer, Ursula; Weißflog, Grit; Volkmer, Ines; Burdach, Stefan; Richter, Günther; Mauz‐Körholz, Christine; Föll, Jürgen; Körholz, Dieter

doi:10.1016/j.exphem.2008.02.014

Cited by 37 publications

(49 citation statements)

References 56 publications

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“…13,14 Despite these advances, however, the mechanisms underlying primary refractory disease and relapse remain largely elusive. In HL cell lines, differences between the gene expression profiles of chemotherapy-resistant and -sensitive cells have been described, 15 and in another study protein kinase C expression was associated with drug resistance in L428 cells. 16 Overall, perhaps related to small case numbers and incomplete clinical data, no investigations of primary HRS cells have been reported yielding definitive target genes that could be linked to a drug resistance phenotype.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome

Steidl¹,

Telenius²,

Shah³

et al. 2010

Blood

161

119

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In classical Hodgkin lymphoma (cHL) the mechanisms underlying primary refractory disease and relapse remain unknown. To gain further insight into cHL pathogenesis and genomic changes linked to treatment response, we studied 53 cHL patients by array comparative genomic hybridization, including 23 patients whose primary treatment failed, using DNA from microdissected HRS cells. Copy number alterations found in more than 20% of cases included gains of 2p, 9p, 16p, 17q, 19q, 20q, and losses of 6q, 11q, and 13q. We identified at high resolution recurrent changes defining minimally gained and lost regions harboring genes involved in nuclear factor B signaling, such as REL, IKBKB, CD40, and MAP3K14. Gains of chromosome 16p11.2-13.3 were significantly more frequent in pretreatment and relapse biopsies of unresponsive patients and were associated with shortened disease-specific survival (P ‫؍‬ .028). In the therapyresistant HL cell line KMH2, we found genomic gains and overexpression of the multidrug resistance gene ABCC1 mapping to cytoband 16p13.11. We show that doxorubicin exposure to KMH2 induces ABCC1 expression and that siRNA silencing of ABCC1 sensitizes KMH2 cells to doxorubicin toxicity in vitro, suggesting that overexpression of ABCC1 contributes to the drug resistance phenotype found in KMH2. (Blood. 2010;116(3): 418-427)

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Section: Introductionmentioning

confidence: 99%

Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome

Steidl¹,

Telenius²,

Shah³

et al. 2010

Blood

161

119

View full text Add to dashboard Cite

show abstract

“…Van Baren [24] detected PRAME in only 1 of 7 patients. On the other hand, Staege et al [16] detected PRAME expression only in patients with resistant HL [31,32] . Willenbrock et al [18] found very high PRAME expression in cases with HL as compared with patients with anaplastic large cell lymphoma and B-cell non-Hodgkin lymphoma.…”

Section: Discussionmentioning

confidence: 99%

“…With these results we can suggest that especially when a PRAME study is planned in fresh tissues in HL, it would be useful to perform the PRAME study by separating these cells by microdissection. PRAME may be a potential target for therapeutic approaches in the future if it is detected in larger series where PRAME is expressed at high rates in resistant HL [16] . On the other hand, high PRAME expression has been found to be associated with increased resistance to chemotherapy in diffuse large B cell lymphoma and in HL.…”

Section: Discussionmentioning

confidence: 99%

“…The basic principle of immunotherapy is the determination of the ideal target and this target should be expressed in tumor cells only but not in normal tissues. From this point of view, PRAME has become a promising candidate for tumor immunotherapy since it is recognized by autologous cytotoxic T lymphocytes [3,16] .…”

Section: Discussionmentioning

confidence: 99%

“…Information about PRAME expression and its prognostic value in HL is very limited. In a study performed by Staege et al [16] it was demonstrated that PRAME has been found to be expressed only in cell lines belonging to patients with resistant HL [17] . In the study performed by Willenbrock et al [18] , when patients with HL were compared with those with anaplastic large cell lymphomas and B cell non-Hodgkin lymphoma, PRAME expression was found to be higher in HL.…”

Section: Prame Expression and Its Clinicalmentioning

confidence: 99%

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PRAME Expression and Its Clinical Relevance in Hodgkin's Lymphoma

Erçolak¹,

Paydaş²,

Bağır³

et al. 2015

Acta Haematol

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Objectives: Although Hodgkin's lymphoma (HL) is one of the most curable cancers in adult patients, new targets have to be defined in cases resistant to traditional chemotherapy. The preferentially expressed antigen of melanoma (PRAME) is a cancer testis antigen and its expression is very scarce or absent in normal tissues. For this reason PRAME is a promising candidate for tumor immunotherapy. The aim of this study is to understand the correlation of PRAME expression with prognostic factors in HL, to determine the utility of PRAME as a targeted molecule for immunotherapy and to compare real-time polymerase chain reaction (real-time PCR) and immunohistochemistry (IHC) for the detection of PRAME. Methods: In 82 patients, PRAME was studied using real-time PCR and IHC. Data analyses were performed using statistical methods such as t test, Mann-Whitney U test, χ² test, Kaplan-Meier method, log-rank test and Cox regression analysis. Results: PRAME was detected in 15 (18.3%) patients using IHC and in 8 (9.8%) patients using real-time PCR. A correlation was found between PRAME positivity and higher International Prognostic Score (p = 0.039). PRAME positivity detected using real-time PCR was found to be correlated with shorter disease-free survival (DFS) and overall survival (OS, p = 0.0005). Discussion: The demonstration of PRAME especially in histiocytes and Reed-Sternberg cells may provide guidance for immunotherapy. Although PRAME positivity increases the risk for death (3.56), independent risk factors that affected DFS and OS occurred in advanced age and high-risk groups. Conclusion: Although real-time PCR is sensitive in the detection of PRAME, IHC can be another useful method. Despite the need for studies conducted on larger patient samples, PRAME expression is considered as a poor prognostic parameter in HL.

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Hodgkin’s lymphoma RNA-transfected dendritic cells induce cancer/testis antigen-specific immune responses

Winkler

Steingrube

Altermann

et al. 2012

Cancer Immunol Immunother

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Gene expression profiles of Hodgkin's lymphoma cell lines with different sensitivity to cytotoxic drugs

Cited by 37 publications

References 56 publications

Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome

Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome

PRAME Expression and Its Clinical Relevance in Hodgkin's Lymphoma

Hodgkin’s lymphoma RNA-transfected dendritic cells induce cancer/testis antigen-specific immune responses

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