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Sökning: WFRF:(Apollonio Benedetta) > (2016) > 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

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.
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.
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.
Galigalidou, Chrysi (författare)
Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece.
Fonte, Eleonora (författare)
IRCCS San Raffaele Sci Inst, Div Expt Oncol, I-20132 Milan, Italy.
Anagnostopoulos, Achilles (författare)
George Papanikolaou Hosp, Dept Hematol, Thessaloniki 57010, Greece.;George Papanikolaou Hosp, Hematopoiet Cell Transplantat Unit, Thessaloniki 57010, Greece.
Belessi, Chrysoula (författare)
Nikea Gen Hosp, Dept Hematol, Piraeus 18454, Greece.
Muzio, Marta (författare)
IRCCS San Raffaele Sci Inst, Div Expt Oncol, I-20132 Milan, Italy.
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.
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.
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 196:10, s. 4410-4417
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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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