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B Cell Anergy Modul...
B Cell Anergy Modulated by TLR1/2 and the miR-17 similar to 92 Cluster Underlies the Indolent Clinical Course of Chronic Lymphocytic Leukemia Stereotyped Subset #4
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- Ntoufa, Stavroula (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece.;George Papanikolaou Hosp, Dept Hematol, Thessaloniki 57010, Greece.;George Papanikolaou Hosp, Hematopoiet Cell Transplantat Unit, Thessaloniki 57010, Greece.
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- Papakonstantinou, Nikos (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece.;George Papanikolaou Hosp, Dept Hematol, Thessaloniki 57010, Greece.;George Papanikolaou Hosp, Hematopoiet Cell Transplantat Unit, Thessaloniki 57010, Greece.
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- Apollonio, Benedetta (författare)
- IRCCS San Raffaele Sci Inst, Div Expt Oncol, I-20132 Milan, Italy.
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- Gounari, Maria (författare)
- IRCCS San Raffaele Sci Inst, Div Expt Oncol, I-20132 Milan, Italy.
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- Galigalidou, Chrysi (författare)
- Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece.
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- Fonte, Eleonora (författare)
- IRCCS San Raffaele Sci Inst, Div Expt Oncol, I-20132 Milan, Italy.
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- Anagnostopoulos, Achilles (författare)
- George Papanikolaou Hosp, Dept Hematol, Thessaloniki 57010, Greece.;George Papanikolaou Hosp, Hematopoiet Cell Transplantat Unit, Thessaloniki 57010, Greece.
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- Belessi, Chrysoula (författare)
- Nikea Gen Hosp, Dept Hematol, Piraeus 18454, Greece.
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- Muzio, Marta (författare)
- IRCCS San Raffaele Sci Inst, Div Expt Oncol, I-20132 Milan, Italy.
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- Ghia, Paolo (författare)
- IRCCS San Raffaele Sci Inst, Div Expt Oncol, I-20132 Milan, Italy.;Univ Vita Salute San Raffaele, Dept Oncohematol, Lymphoma Unit, I-20132 Milan, Italy.
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- Stamatopoulos, Kostas (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece.;George Papanikolaou Hosp, Dept Hematol, Thessaloniki 57010, Greece.;George Papanikolaou Hosp, Hematopoiet Cell Transplantat Unit, Thessaloniki 57010, Greece.
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Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece;George Papanikolaou Hosp, Dept Hematol, Thessaloniki 57010, Greece.;George Papanikolaou Hosp, Hematopoiet Cell Transplantat Unit, Thessaloniki 57010, Greece. IRCCS San Raffaele Sci Inst, Div Expt Oncol, I-20132 Milan, Italy. (creator_code:org_t)
- 2016-05-15
- 2016
- Engelska.
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 196:10, s. 4410-4417
- Relaterad länk:
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https://www.jimmunol...
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https://urn.kb.se/re...
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https://doi.org/10.4...
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Abstract
Ämnesord
Stäng
- Chronic lymphocytic leukemia (CLL) patients assigned to stereotyped subset #4 (mutated IGHV4-34/IGKV2-30 BCR Ig) display a particularly indolent disease course. Immunogenetic studies of the clonotypic BCR Ig of CLL subset #4 suggested a resemblance with B cells rendered anergic through chronic autoantigenic stimulation. In this article, we provide experimental evidence that subset #4 CLL cells show low IgG levels, constitutive ERK1/2 activation, and fail to either release intracellular Ca2+ or activate MAPK signaling after BCR cross-linking, thus displaying a signature of B cell anergy at both biochemical and functional levels. Interestingly, TLR1/2 triggering restored BCR functionality, likely breaching the anergic state, and this was accompanied by induction of the miR17 similar to 92 cluster, whose members target critical BCR-associated molecules, including MAPKs. In conclusion, we demonstrate BCR anergy in CLL subset #4 and implicate TLR signaling and the miR-17 similar to 92 cluster in the regulation of the anergic state. This detailed signaling profiling of subset #4 has implications for advanced understanding of the complex regulation of intracellular signaling pathways in CLL, currently a major therapeutic target of the disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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Ntoufa, Stavroul ...
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Papakonstantinou ...
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Apollonio, Bened ...
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Gounari, Maria
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Galigalidou, Chr ...
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Fonte, Eleonora
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Anagnostopoulos, ...
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Belessi, Chrysou ...
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Muzio, Marta
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Ghia, Paolo
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Stamatopoulos, K ...
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