Expression of CD27–CD70 on Early B Cell Progenitors in the Bone Marrow: Implication for Diagnosis and Therapy of Childhood ALL

Nilsson, Anna; Milito, Angelo De; Mowafi, Frida; Winberg, Gösta; Björk, Olle; Wolpert, Elisabeth Z.; Chiodi, Francesca

doi:10.1016/j.exphem.2005.10.005

Cited by 52 publications

(49 citation statements)

References 32 publications

(36 reference statements)

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“…sCD27 can induce proliferation in CD70-positive acute lymphoblastic leukemia and nasal NK/T-cell lymphoma (40,41). It was therefore tempting to speculate that the interaction of CD27…”

Section: Discussionmentioning

confidence: 99%

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pVHL/HIF-Regulated CD70 Expression Is Associated with Infiltration of CD27+ Lymphocytes and Increased Serum Levels of Soluble CD27 in Clear Cell Renal Cell Carcinoma

Ruf

Mittmann

Nowicka

et al. 2015

Clinical Cancer Research

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Purpose: CD70, a member of the TNF ligand superfamily, has been shown frequently overexpressed in clear cell renal cell carcinoma (ccRCC). The mechanisms of CD70's upregulation and its role in ccRCC are unknown.Experimental Design: CD70 expression was immunohistochemically analyzed in 667 RCCs and RCC metastases. Von Hippel-Lindau gene (VHL) mutations, expression patterns of VHL protein (pVHL), hypoxia-inducible factor (HIF) a, and several HIF targets were studied in tissues and cell lines and correlated with CD70 overexpression. Gene promoter analysis was performed to confirm CD70 as HIF target gene. Consecutive tissue sections were immunostained to reveal the relation between CD70-expressing RCCs and tumor-infiltrating lymphocytes positive for the CD70 receptor (CD27). CD70-mediated release of soluble CD27 in RCC was assessed by coculture experiments and sera analysis of patients with RCC.

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“…sCD27 can induce proliferation in CD70-positive acute lymphoblastic leukemia and nasal NK/T-cell lymphoma (40,41). It was therefore tempting to speculate that the interaction of CD27…”

Section: Discussionmentioning

confidence: 99%

“…Besides lymphoid malignancies (40,41), ccRCC is the first solid tumor type in which increased serum levels of sCD27 have been observed. High serum concentration of sCD27 may thus represent a potential predictive marker in patients with ccRCC, which indirectly indicates the presence of CD70-expressing tumors.…”

Section: Discussionmentioning

confidence: 99%

pVHL/HIF-Regulated CD70 Expression Is Associated with Infiltration of CD27+ Lymphocytes and Increased Serum Levels of Soluble CD27 in Clear Cell Renal Cell Carcinoma

Ruf

Mittmann

Nowicka

et al. 2015

Clinical Cancer Research

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“…Omeprazole (0-200 Amol/L) was added the next day, and apoptosis was measured 2 days after treatment. The analysis was done on the gate of bone marrow cells previously shown to be represented by >90% CD19 + leukemic cells (26). Lysosomal stability assessment.…”

Section: Methodsmentioning

confidence: 99%

Proton Pump Inhibitors Induce Apoptosis of Human B-Cell Tumors through a Caspase-Independent Mechanism Involving Reactive Oxygen Species

et al. 2007

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Proton pumps like the vacuolar-type H + ATPase (V-ATPase) are involved in the control of cellular pH in normal and tumor cells. Treatment with proton pump inhibitors (PPI) induces sensitization of cancer cells to chemotherapeutics via modifications of cellular pH gradients. It is also known that low pH is the most suitable condition for a full PPI activation. Here, we tested whether PPI treatment in unbuffered culture conditions could affect survival and proliferation of human B-cell tumors. First, we showed that PPI treatment increased the sensitivity to vinblastine of a pre-B acute lymphoblastic leukemia (ALL) cell line. PPI, per se, induced a dose-dependent inhibition of proliferation of tumor B cells, which was associated with a dose-and time-dependent apoptotic-like cytotoxicity in B-cell lines and leukemic cells from patients with pre-B ALL. The effect of PPI was mediated by a very early production of reactive oxygen species (ROS), that preceded alkalinization of lysosomal pH, lysosomal membrane permeabilization, and cytosol acidification, suggesting an early destabilization of the acidic vesicular compartment. Lysosomal alterations were followed by mitochondrial membrane depolarization, release of cytochrome c, chromatin condensation, and caspase activation. However, inhibition of caspase activity did not affect PPI-induced cell death, whereas specific inhibition of ROS by an antioxidant (N-acetylcysteine) significantly delayed cell death and protected both lysosomal and mitochondrial membranes. The proapoptotic activity of PPI was consistent with a clear inhibition of tumor growth following PPI treatment of B-cell lymphoma in severe combined immunodeficient mice. This study further supports the importance of acidity and pH gradients in tumor cell homeostasis and suggests new therapeutic approaches for human B-cell tumors based on PPI. [Cancer Res 2007;67(11):5408-17]

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“…In these mature B cell malignancies, deregulated and increased CD70 expression has been found on most CLL and mature lymphoma subtypes. This is in contrast to acute lymphoblastic leukemia (ALL), the most common childhood malignancy, where only low-level expression of CD70 on B cell precursor blasts has been documented (28). Given the differential baseline expression pattern of CD70 in immature vs mature B cell malignancies, it is in fact critical to investigate under which conditions the expression level of CD70 becomes increased on immature ALL blasts in view of enhancing cytotoxic antileukemic T cell response.…”

mentioning

confidence: 99%

The CD70/CD27 Pathway Is Critical for Stimulation of an Effective Cytotoxic T Cell Response against B Cell Precursor Acute Lymphoblastic Leukemia

Glouchkova

Ackermann

Zibert

et al. 2009

The Journal of Immunology

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For effective immunotherapy, maintaining the frequency and cytotoxic potential of effector cells is critical. In this context costimulation via the CD70/CD27 pathway has been proven essential. CD70 has been reported to be expressed to varying degrees on malignant B cells. However, in B cell precursor acute lymphboblastic leukemia, the most common childhood malignancy, the role of CD70 in stimulation of antileukemic T cell responses has so far not been delineated. Herein we demonstrate that in B cell precursor acute lymphboblastic leukemia expression of CD70 is low but can be induced upon blast activation via CD40. Both CD70 and CD80/CD86 up-regulated on CD40-stimulated blasts contribute to primary stimulation of T cell proliferation and cytokine production in an additive manner. These two signals also cooperate in the prevention of T cell anergy. In contrast to blockade of CD70 during the effector phase, inhibition of CD70-mediated costimulation during generation of antileukemic T cells prevents effector cell proliferation and reduces their cytotoxic capacity. Modulation of the CD70/CD27 pathway may thus represent a novel therapeutic approach for augmenting magnitude and quality of the antileukemic response in B cell precursor acute lymphboblastic leukemia.

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Expression of CD27–CD70 on Early B Cell Progenitors in the Bone Marrow: Implication for Diagnosis and Therapy of Childhood ALL

Cited by 52 publications

References 32 publications

pVHL/HIF-Regulated CD70 Expression Is Associated with Infiltration of CD27+ Lymphocytes and Increased Serum Levels of Soluble CD27 in Clear Cell Renal Cell Carcinoma

pVHL/HIF-Regulated CD70 Expression Is Associated with Infiltration of CD27+ Lymphocytes and Increased Serum Levels of Soluble CD27 in Clear Cell Renal Cell Carcinoma

Proton Pump Inhibitors Induce Apoptosis of Human B-Cell Tumors through a Caspase-Independent Mechanism Involving Reactive Oxygen Species

The CD70/CD27 Pathway Is Critical for Stimulation of an Effective Cytotoxic T Cell Response against B Cell Precursor Acute Lymphoblastic Leukemia

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