CD38+ chronic lymphocytic leukaemia cells co-express high levels of ZAP-70 and are functionally distinct from their CD38− counter-parts

Pepper, Chris; Brennan, Paul; Alghazal, Suhair; Ward, Rachel; Pratt, Guy; Starczynski, Jane; Lin, T; Rowntree, C; Fegan, Christopher

doi:10.1038/sj.leu.2404133

Cited by 12 publications

(11 citation statements)

References 9 publications

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“…32 We have shown that expression of ZAP-70 can be induced together with CD38 expression by the CD154/IL-4 system (Supplementary Table 2) in a proportion of patients, although others show discordance in the induction of these two molecules ( Figure 8A and 8B). CD40 stimulation, therefore, appears to play a role in driving expression of both CD38 and ZAP-70 but other factors, some of which may be intrinsic to the leukemic cell, also function to regulate the expression of these prognostically important proteins.…”

Section: -47mentioning

confidence: 99%

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Regulation of CD38 in proliferating chronic lymphocytic leukemia cells stimulated with CD154 and interleukin-4

Willimott¹,

Baou²,

Huf³

et al. 2007

Haematologica

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Section: -47mentioning

confidence: 99%

“…It has been reported that CLL cells co-express CD38 and ZAP-70 32 and also that some of the effects of CD38 signaling may be mediated through ZAP-70 phosphorylation.…”

Section: Relationship Of Zap-70 Expression To Cd38 Expressionmentioning

confidence: 99%

Regulation of CD38 in proliferating chronic lymphocytic leukemia cells stimulated with CD154 and interleukin-4

Willimott¹,

Baou²,

Huf³

et al. 2007

Haematologica

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“…14,59,60 The same phenomena are observed at the intraclonal level as CD38 ϩ cells respond more readily to BCR stimulation than CD38 Ϫ cells of the same clone. 57,73 However, evidence for involvement of CD38 in the BCR signaling pathway is indirect and linked to lateral associations with CD19 and CD81 (in turn part of the BCR complex) and colocalization in the same lipid rafts as the BCR. 26 The most favorable conditions for expansion of CLL clones exist in discrete anatomic sites, such as PCs in LN and in the BM, where leukemic cells come into contact with accessory cells and the appropriate array of cytokines and chemokines.…”

Section: Cd38-mediated Signals and Their Connection With The Bcrmentioning

confidence: 99%

CD38 and chronic lymphocytic leukemia: a decade later

Malavasi

Deaglio

Damle

et al. 2011

Blood

196

160

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This review highlights a decade of investigations into the role of CD38 in CLL. CD38 is accepted as a dependable marker of unfavorable prognosis and as an indicator of activation and proliferation of cells when tested. Leukemic clones with higher numbers of CD38 ؉ cells are more responsive to BCR signaling and are characterized by enhanced migration. In vitro activation through CD38 drives CLL proliferation and chemotaxis via a signaling pathway that includes ZAP-70 and ERK1/2. Finally, CD38 is under a polymorphic transcriptional control after external signals.Consequently, CD38 appears to be a global molecular bridge to the environment, promoting survival/proliferation over apoptosis. Together, this evidence contributes to the current view of CLL as a chronic disease in which the host's microenvironment promotes leukemic cell growth and also controls the sequential acquisition and accumulation of genetic alterations. This view relies on the existence of a set of surface molecules, including CD38, which support proliferation and survival of B cells on their way to and after neoplastic transformation. The second decade of studies on CD38 in CLL will tell if the molecule is an effective target for antibody-mediated therapy in this currently incurable leukemia. (Blood. 2011;118(13):3470-3478)The current view of chronic lymphocytic leukemia (CLL) is that of a disease characterized by a dynamic balance between cells circulating in the blood and cells located in permissive niches in lymphoid organs. 1 The former are primarily mature-looking small lymphocytes resistant to apoptosis, whereas the latter are composed of lymphocytes that undergo either proliferation or apoptosis according to the environment. 2 The heterogeneous clinical outcome of CLL patients is dictated, at least in part, by the nature of these microenvironmental signals and interactions that can promote or impair accumulation of genomic alterations. 3 Detailed immunophenotypic and genetic analyses of different neoplastic clones have led to the identification of a number of molecular markers, some of which are gaining relevance in clinical practice to predict disease outcome. [4][5][6][7] Cell surface CD38 is one of these markers.This review highlights a decade of investigations into the role of CD38 in CLL. An association between CD38 expression by CLL cells and a more aggressive clinical behavior was first reported in 1999 4 and confirmed by several subsequent studies. [8][9][10][11][12] Consequently, determination of the percentage of CD38-expressing cells within a clone has become part of the workup of CLL patients in many clinical centers, 13 and it is generally accepted that CD38 ϩ patients will have a shorter progression-free interval, require earlier and more frequent treatments, and ultimately die sooner. 4 The underlying question behind these clinical observations is why expression of this molecule on the cell surface would correlate with a worse clinical outcome. The most obvious possibility is that CD38 expression reflects events occurring in...

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“…18 It is therefore likely that multiple, dynamic, mechanisms exist for the control of Mcl-1 expression in CLL cells but autocrine VEGF is a critical determinant of basal expression. Several recent studies have shown that CD38 expression is higher in CLL cells in the bone marrow and lymphoid tissues when compared to peripheral blood.…”

Section: Cd38 Expression In Cll C Pepper Et Almentioning

confidence: 99%

“…14 Several groups have suggested that CD38 may be involved in signaling through the B-cell receptor (BCR) in CLL, [15][16][17] and in this regard we have recently shown an association between CD38 expression and the tyrosine kinase ZAP-70. 18 Furthermore, a recent study has shown an association between CD38 expression, activation marker expression and differential responses to interferon stimulation. 19 In this study, we isolated CD38 þ and CD38 À sub-populations from patients with bimodal expression of the CD38 antigen to elucidate a biological mechanism for the adverse impact of CD38 expression in CLL.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

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CD38+ chronic lymphocytic leukaemia cells co-express high levels of ZAP-70 and are functionally distinct from their CD38− counter-parts

Cited by 12 publications

References 9 publications

Regulation of CD38 in proliferating chronic lymphocytic leukemia cells stimulated with CD154 and interleukin-4

Regulation of CD38 in proliferating chronic lymphocytic leukemia cells stimulated with CD154 and interleukin-4

CD38 and chronic lymphocytic leukemia: a decade later

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

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