Coexpression of CD44 variant isoforms and receptor for hyaluronic acid−mediated motility (RHAMM, CD168) is an International Prognostic Index and C-MYC gene status−independent predictor of poor outcome in diffuse large B-cell lymphomas

Nagel, Sabine; Hirschmann, Petra; Dirnhofer, Stephan; Günthert, Ursula; Tzankov, Alexandar

doi:10.1016/j.exphem.2009.10.010

Cited by 33 publications

(26 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD44s represents standard form of translated 10 of 20 exons of theCD44 gene, whose other 10 exons are spliced into variant isoforms (CD44v) which are mostly expressed on malignant cells [23,24]. Previous studies have reported that CD44s and CD44 variants correlate with advanced stage of DLBCL and worst outcome [48]. As suggested, CD44s clustered with typical non-GCB DLBCL markers, which however is not confirmed in our study [31].…”

Section: Discussionmentioning

confidence: 40%

The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas

Jelicic

Balint

Jovanović³

et al. 2016

Pathol. Oncol. Res.

View full text Add to dashboard Cite

Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC >2.6 in DLBCL and ALC/AMC ≥ 4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p < 0.05). In DLBCL, MVD > 42 blood vessels/0.36 mm(2) correlated with primary resistant disease (p < 0.0001), poorer EFS and OS (p = 0.014). High CD44s expression in FL correlated with inferior EFS and OS (p < 0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51-7.09, p = 0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08-1.79, p = 0.01). Furthermore, in FL, ALC/AMC mostly influenced OS (HR 5.21, 95 % CI 1.17-23.21, p = 0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06-14.95, p = 0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s).

show abstract

Section: Discussionmentioning

confidence: 40%

The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas

Jelicic

Balint

Jovanović³

et al. 2016

Pathol. Oncol. Res.

View full text Add to dashboard Cite

show abstract

“…In DLBCL co-expression of CD44v and HA-mediated motility receptor (RHAMM) leads to unfavorable outcome when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [147]. Similarly in MM, treatment success of Dexamethasone was dependent on CD44 with decreased apoptosis rates in cells with high CD44 [148].…”

Section: Experimental Antagonization and Drug Resistancementioning

confidence: 99%

CD44 in hematological neoplasias

2011

View full text Add to dashboard Cite

“…Previously described tissue microarrays with 249 primary DLBCLs were used in the present study (32). Cases were classified as GCB or non-GCB DLBCL applying the Tally algorithm (33).…”

mentioning

confidence: 99%

PTEN loss defines a PI3K/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma

Pfeifer

Grau

Lenze

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

241

197

View full text Add to dashboard Cite

Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous diagnostic category with distinct molecular subtypes that can be defined by gene expression profiling. However, even within these defined subtypes, heterogeneity prevails. To further elucidate the pathogenesis of these entities, we determined the expression of the tumor suppressor phosphatase and tensin homolog (PTEN) in 248 primary DLBCL patient samples. These analyses revealed that loss of PTEN was detectable in 55% of germinal center B-cell-like (GCB) DLBCLs, whereas this abnormality was found in only 14% of non-GCB DLBCL patient samples. In GCB DLBCL, the PTEN status was inversely correlated with activation of the oncogenic PI3K/ protein kinase B (AKT) pathway in both DLBCL cell lines and primary patient samples. Reexpression of PTEN induced cytotoxicity in PTEN-deficient GCB DLBCL cell line models by inhibiting PI3K/AKT signaling, indicating an addiction to this pathway in this subset of GCB DLBCLs. PI3K/AKT inhibition induced down-regulation of the transcription factor MYC. Reexpression of MYC rescued GCB DLBCL cells from PTEN-induced toxicity, identifying a regulatory mechanism of MYC expression in DLBCL. Finally, pharmacologic PI3K inhibition resulted in toxicity selectively in PTEN-deficient GCB DLBCL lines. Collectively, our results indicate that PTEN loss defines a PI3K/ AKT-dependent GCB DLBCL subtype that is addicted to PI3K and MYC signaling and suggest that pharmacologic inhibition of PI3K might represent a promising therapeutic approach in these lymphomas. Diffuse large B-cell lymphoma (DLBCL) represents the most frequent lymphoma subtype and is considered a heterogeneous diagnostic category (1). Using gene expression profiling, two major molecular subtypes can be distinguished termed germinal center B-cell-like (GCB) DLBCL and activated B-cell-like (ABC) DLBCL (2). GCB DLBCLs are derived from germinal center B cells, whereas ABC DLBCLs originate from postgerminal center B cells that are in the transition of being differentiated into plasma cells. However, full plasma cell maturation is blocked in ABC DLBCL by different genetic abnormalities inhibiting the function of BLIMP1 that regulates plasmacytic differentiation (3-5).Recent work suggested constitutive activation of the PI3K/ protein kinase B (AKT) pathway that plays a crucial role in mediating growth, proliferation, and cell survival in a substantial number of DLBCL patient samples determined by immunohistochemical staining for phospho-AKT (p-AKT) (6, 7). However, these studies did not investigate the molecular mechanisms leading to constitutive PI3K/AKT signaling. The tumor suppressor PTEN is the major negative regulator of PI3K/AKT. PTEN functions as a lipid phosphatase dephosphorylating the 3′ position of phosphatidyl-inositol-3,-4,-5-trisphosphate, which serves as a trigger for AKT activation (8, 9). However, recent studies showed that PTEN has additional PI3K/AKT-independent tumor suppressor functions. Nuclear PTEN, for example, acts as guardian of genome integrity by up-...

show abstract

Coexpression of CD44 variant isoforms and receptor for hyaluronic acid−mediated motility (RHAMM, CD168) is an International Prognostic Index and C-MYC gene status−independent predictor of poor outcome in diffuse large B-cell lymphomas

Cited by 33 publications

References 36 publications

The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas

The Role of Lymphocyte to Monocyte Ratio, Microvessel Density and HiGH CD44 Tumor Cell Expression in Non Hodgkin Lymphomas

CD44 in hematological neoplasias

PTEN loss defines a PI3K/AKT pathway-dependent germinal center subtype of diffuse large B-cell lymphoma

Contact Info

Product

Resources

About