BAFF and APRIL expression in B-cell chronic lymphocytic leukemia: Correlation with biological and clinical features

Bojarska‐Junak, Agnieszka; Hus, Iwona; Chocholska, Sylwia; Wąsik-Szczepanek, Ewa; Sieklucka, Małgorzata; Dmoszyńska, Anna; Roliński, Jacek

doi:10.1016/j.leukres.2009.03.030

Cited by 43 publications

(54 citation statements)

References 27 publications

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“…Interestingly, CLL MSC supernatants show higher levels of APRIL, as previously mentioned, and lower levels of BAFF as compared with supernatants from healthy donors. These findings are in accordance with plasma levels of the respective molecules in CLL patients [43,45,47,48]. Whether the observed differences in the production of BAFF, APRIL, and SDF-1, as previously mentioned, between patient-derived MSCs and healthy donor-derived MSCs, bear important functional consequences for CLL cells is an issue that still remains open.…”

supporting

confidence: 85%

Study of the Quantitative, Functional, Cytogenetic, and Immunoregulatory Properties of Bone Marrow Mesenchymal Stem Cells in Patients with B-Cell Chronic Lymphocytic Leukemia

Pontikoglou

Kastrinaki²,

Klaus³

et al. 2013

Stem Cells and Development

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supporting

confidence: 85%

Study of the Quantitative, Functional, Cytogenetic, and Immunoregulatory Properties of Bone Marrow Mesenchymal Stem Cells in Patients with B-Cell Chronic Lymphocytic Leukemia

Pontikoglou

Kastrinaki²,

Klaus³

et al. 2013

Stem Cells and Development

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“…Additionally, our studies also observed that BAFF/APRIL-related genes were also enriched in LN-CLL cells. These genes have been shown to promote cell survival and adverse prognosis in CLL (31,43). These observations suggest that LN sites provide signals for chronic activation of CLL cells.…”

Section: Discussionmentioning

confidence: 85%

Chronic Lymphocytic Leukemia Cells in a Lymph Node Microenvironment Depict Molecular Signature Associated with an Aggressive Disease

Mittal

Chaturvedi

Karan

et al. 2014

Mol Med

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Chronic lymphocytic leukemia (CLL) cells survive longer in vivo than in vitro, suggesting that the tissue microenvironment provides prosurvival signals to tumor cells. Primary and secondary lymphoid tissues are involved in the pathogenesis of CLL, and the role of these tissue microenvironments has not been explored completely. To elucidate host-tumor interactions, we performed gene expression profiling (GEP) of purified CLL cells from peripheral blood (PB; n = 20), bone marrow (BM; n = 18), and lymph node (LN; n = 15) and validated key pathway genes by real-time polymerase chain reaction, immunohistochemistry and/or TCL1 transgenic mice. Gene signatures representing several pathways critical for survival and activation of B cells were altered in CLL cells from different tissue compartments. Molecules associated with the B-cell receptor (BCR), B cell-activating factor/a proliferationinducing ligand (BAFF/APRIL), nuclear factor (NF)-κB pathway and immune suppression signature were enriched in LN-CLL, suggesting LNs as the primary site for tumor growth. Immune suppression genes may help LN-CLL cells to modulate antigenpresenting and T-cell behavior to suppress antitumor activity. PB CLL cells overexpressed chemokine receptors, and their cognate ligands were enriched in LN and BM, suggesting that a chemokine gradient instructs B cells to migrate toward LN or BM. Of several chemokine ligands, the expression of CCL3 was associated with poor prognostic factors. The BM gene signature was enriched with antiapoptotic, cytoskeleton and adhesion molecules. Interestingly, PB cells from lymphadenopathy patients shared GEP with LN cells. In Eμ-TCL1 transgenic mice (the mouse model of the disease), a high percentage of leukemic cells from the lymphoid compartment express key BCR and NF-κB molecules. Together, our findings demonstrate that the lymphoid microenvironment promotes survival, proliferation and progression of CLL cells via chronic activation of BCR, BAFF/APRIL and NF-κB activation while suppressing the immune response.

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“…Although it is known that BAFF levels in plasma are not elevated in CLL patients relative to levels in normal individuals (26), BAFF concentrates on the cell surface of NLC at much higher amounts than on CLL cells (19). NLC are found in the spleen and secondary lymphoid tissues of CLL patients (20), where they presumably protect CLL cells from apoptosis (19,20).…”

Section: Discussionmentioning

confidence: 99%

B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia

Zhang

Kater

Widhopf³

et al. 2010

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

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Mice bearing a v-Myc myelocytomatosis viral oncogene homolog ( c-Myc ) transgene controlled by an Ig-alpha heavy-chain enhancer (i Myc Cα mice) rarely develop lymphomas but instead have increased rates of memory B-cell turnover and impaired antibody responses to antigen. We found that male progeny of i Myc Cα mice mated with mice transgenic (Tg) for CD257 (B-cell activating factor, BAFF) developed CD5 + B-cell leukemia resembling human chronic lymphocytic leukemia (CLL), which also displays a male gender bias. Surprisingly, leukemic cells of Myc/Baff Tg mice expressed higher levels of c-Myc than did B cells of i Myc Cα mice. We found that CLL cells of many patients with progressive disease also expressed high amounts of c-MYC, particularly CLL cells whose survival depends on nurse-like cells (NLC), which express high-levels of BAFF. We find that BAFF could enhance CLL-cell expression of c-MYC via activation the canonical IκB kinase (IKK)/NF-κB pathway. Inhibition of the IKK/NF-κB pathway in mouse or human leukemia cells blocked the capacity of BAFF to induce c-MYC or promote leukemia-cell survival and significantly impaired disease progression in Myc/Baff Tg mice. This study reveals an important relationship between BAFF and c-MYC in CLL which may affect disease development and progression, and suggests that inhibitors of the canonical NF-κB pathway may be effective in treatment of patients with this disease.

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BAFF and APRIL expression in B-cell chronic lymphocytic leukemia: Correlation with biological and clinical features

Cited by 43 publications

References 27 publications

Study of the Quantitative, Functional, Cytogenetic, and Immunoregulatory Properties of Bone Marrow Mesenchymal Stem Cells in Patients with B-Cell Chronic Lymphocytic Leukemia

Study of the Quantitative, Functional, Cytogenetic, and Immunoregulatory Properties of Bone Marrow Mesenchymal Stem Cells in Patients with B-Cell Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Cells in a Lymph Node Microenvironment Depict Molecular Signature Associated with an Aggressive Disease

B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia

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