Highly purified CD38+ and CD38− sub-clones derived from the same chronic lymphocytic leukemia patient have distinct gene expression signatures despite their monoclonal origin

Pepper, Chris; Ward, Rachel; Lin, T; Brennan, Paul; Starczynski, Jane; Musson, Megan; Rowntree, C; Bentley, Paul; Mills, Ken I.; Pratt, Guy; Fegan, Christopher

doi:10.1038/sj.leu.2404587

Cited by 47 publications

(42 citation statements)

References 45 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3B), showing that, in vivo, a small subset of circulating CLL cells expressed lower levels of S1PR1 compared with the rest of the leukemic clone. Additionally, when we evaluated S1PR1 expression in bone marrow-resident CLL cells segregated based on the surface expression of CD38, which defines a subpopulation of activated lymphocytes (38,40), we found that, in all of the patients evaluated (Table I), bone marrow leukemic cells expressing high levels of CD38 showed a reduced expression of S1PR1 compared with CD38 low/2 counterparts (Fig. 3C).…”

Section: Resultsmentioning

confidence: 94%

The Expression of Sphingosine-1 Phosphate Receptor-1 in Chronic Lymphocytic Leukemia Cells Is Impaired by Tumor Microenvironmental Signals and Enhanced by Piceatannol and R406

Borge

Lenicov

Nannini

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Chronic lymphocytic leukemia (CLL) is characterized by the progressive accumulation of clonal B lymphocytes. Proliferation occurs in lymphoid tissues upon interaction of leukemic cells with a supportive microenvironment. Therefore, the mobilization of tissue-resident CLL cells into the circulation is a useful therapeutic strategy to minimize the reservoir of tumor cells within survival niches. Because the exit of normal lymphocytes from lymphoid tissues depends on the presence of sphingosine-1 phosphate (S1P) and the regulated expression of S1P receptor-1 (S1PR1), we investigated whether the expression and function of S1PR1 can be modulated by key microenvironment signals. We found that activation of CLL cells with CXCL12, fibroblast CD40L+, BCR cross-linking, or autologous nurse-like cells reduces their S1PR1 expression and the migratory response toward S1P. Moreover, we found that S1PR1 expression was reduced in the proliferative/activated subset of leukemic cells compared with the quiescent subset from the same patient. Similarly, bone marrow–resident CLL cells expressing high levels of the activation marker CD38 showed a lower expression of S1PR1 compared with CD38low counterparts. Finally, given that treatment with BCR-associated kinase inhibitors induces a transient redistribution of leukemic cells from lymphoid tissues to circulation, we studied the effect of the Syk inhibitors piceatannol and R406 on S1PR1 expression and function. We found that they enhance S1PR1 expression in CLL cells and their migratory response toward S1P. Based on our results, we suggest that the regulated expression of S1PR1 might modulate the egress of the leukemic clone from lymphoid tissues.

show abstract

Section: Resultsmentioning

confidence: 94%

The Expression of Sphingosine-1 Phosphate Receptor-1 in Chronic Lymphocytic Leukemia Cells Is Impaired by Tumor Microenvironmental Signals and Enhanced by Piceatannol and R406

Borge

Lenicov

Nannini

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The results showed that CD38 pos CLL cells possess a distinct gene expression profile compared with their CD38 neg sub-clones. CD38 pos CLL B-cells relatively overexpress vascular endothelial growth factor (VEGF), which is associated with increased expression of the anti-apoptotic protein Mcl-1 [13]. Detailed characterization of the proliferating CLL B-cell convincingly demonstrated a close association between CD38 expression and increased percentages of Ki-67 and ZAP-70 positive cells, suggesting that CD38 pos clonal members are more highly activated and prone to enter the cell cycle than their negative counterpart [13].…”

Section: Proliferative Cd38 Positive Cll B-cellsmentioning

confidence: 99%

Microenvironment Interactions in Chronic Lymphocytic Leukemia: A Delicate Equilibrium Linking the Quiescent and the Proliferative Pool

Palacios¹,

Abreu²,

Moreno³

et al. 2012

Chronic Lymphocytic Leukemia

View full text Add to dashboard Cite

“…Malignant CLL cells produce VEGF and concomitantly express receptors for this proangiogenic cytokine, thereby creating an autocrine proangiogenic signalling loop. Survival of B-CLL malignant cells is significantly prolonged by VEGF action which is responsible for increased expression of antiapoptic molecule Bcl2 (46). The level of VEGF in CD38 + CLL cells is 2 to 3 times higher compared to CD38 -CLL cells.…”

Section: Angiogenesis In Cllmentioning

confidence: 99%

Biological Prognostic Markers in Chronic Lymphocytic Leukemia

Vroblova

Smolej

Vrbacky

et al. 2009

Acta Med. (Hradec Kralove, Czech Repub.)

View full text Add to dashboard Cite

Summary: Chronic lymphocytic leukemia (CLL) is the most frequent leukemic disease of adults in the Western world. It is remarkable by an extraordinary heterogeneity of clinical course with overall survival ranging from several months to more than 15 years. Classical staging sytems by Rai and Binet, while readily available and useful for initial assessment of prognosis, are not able to determine individual patient's ongoing clinical course of CLL at the time of diagnosis, especially in early stages. Therefore, newer biological prognostic parameters are currently being clinically evaluated. Mutational status of variable region of immunoglobulin heavy chain genes (IgVH), cytogenetic aberrations, and both intracellular ZAP-70 and surface CD38 expression are recognized as parameters with established prognostic value. Molecules regulating the process of angiogenesis are also considered as promising markers. The purpose of this review is to summarize in detail the specific role of these prognostic factors in chronic lymphocytic leukemia.

show abstract

Highly purified CD38+ and CD38− sub-clones derived from the same chronic lymphocytic leukemia patient have distinct gene expression signatures despite their monoclonal origin

Cited by 47 publications

References 45 publications

The Expression of Sphingosine-1 Phosphate Receptor-1 in Chronic Lymphocytic Leukemia Cells Is Impaired by Tumor Microenvironmental Signals and Enhanced by Piceatannol and R406

The Expression of Sphingosine-1 Phosphate Receptor-1 in Chronic Lymphocytic Leukemia Cells Is Impaired by Tumor Microenvironmental Signals and Enhanced by Piceatannol and R406

Microenvironment Interactions in Chronic Lymphocytic Leukemia: A Delicate Equilibrium Linking the Quiescent and the Proliferative Pool

Biological Prognostic Markers in Chronic Lymphocytic Leukemia

Contact Info

Product

Resources

About