Robbe, H W*
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Purpose: Unmutated (UM) immunoglobulin heavy chain variable region (IgHV) status or IgHV3-21 gene usage is associated with poor prognosis in chronic lymphocytic leukemia (CLL) patients. Interestingly, IgHV3-21 is often co-expressed with light chain IgLV3-21, which is potentially able to trigger cell-autonomous BCR-mediated signaling. However, this light chain has never been characterized independently of the heavy chain IgHV3-21.Experimental Design: We performed total RNA sequencing in 32 patients and investigated IgLV3-21 prognostic impact in terms of treatment-free survival (TFS) and overall survival (OS) in 3 other independent cohorts for a total of 813 patients. IgLV3-21 presence was tested by real-time PCR and confirmed by Sanger sequencing.Results: Using total RNA sequencing to characterize 32 patients with high-risk CLL, we found a high frequency (28%) of IgLV3-21 rearrangements. Gene set enrichment analysis revealed that these patients express higher levels of genes responsible for ribosome biogenesis and translation initiation (P < 0.0001) as well as MYC target genes (P = 0.0003). Patients with IgLV3-21 rearrangements displayed a significantly shorter TFS and OS (P < 0.05), particularly those with IgHV mutation. In each of the three independent validation cohorts, we showed that IgLV3-21 rearrangements-similar to UM IgHV status-conferred poor prognosis compared with mutated IgHV (P < 0.0001). Importantly, we confirmed by multivariate analysis that this was independent of IgHV mutational status or subset #2 stereotyped receptor (P < 0.0001).Conclusions: We have demonstrated for the first time that a light chain can affect CLL prognosis and that IgLV3-21 light chain usage defines a new subgroup of CLL patients with poor prognosis. Clin Cancer Res; 24(20); 5048-57. ©2018 AACR.
- MeSH
- chromozomální aberace MeSH
- chronická lymfatická leukemie diagnóza genetika mortalita MeSH
- genová ontologie MeSH
- klinické zkoušky jako téma MeSH
- lehké řetězce imunoglobulinů genetika MeSH
- lidé MeSH
- mutace MeSH
- nádorové biomarkery MeSH
- peptidy genetika MeSH
- prognóza MeSH
- regulace genové exprese u leukemie MeSH
- sekvenční analýza DNA MeSH
- stanovení celkové genové exprese MeSH
- transkriptom MeSH
- variabilní oblast imunoglobulinu genetika MeSH
- výpočetní biologie metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
... Electronic clinical trial protocol distribution via the World-Wide Web: a prototype for reducing costs ... ... Reliability of health information for the public on the World Wide Web: systematic survey of advice on ... ... BMJ 1997;314:1875-9. 180 Wyatt JC. Commentary: measuring quality and impact of the World Wide Web. ... ... M, Muller H, Bahner M, Mei. ... ... J Clin Pathol 1997;50:375-8. 257 Pierik FH, Van Ginneken AM, Timmers T, Stam H, Weber RF. ...
ix, 534 stran : ilustrace, tabulky ; 28 cm
- MeSH
- chorobopisy - počítačové systémy MeSH
- internet MeSH
- management znalostí MeSH
- metody pro podporu rozhodování MeSH
- počítačové zpracování obrazu MeSH
- počítačové zpracování signálu MeSH
- řízení zdravotnictví MeSH
- studium lékařství MeSH
- zdravotnické informační systémy MeSH
- Publikační typ
- sborníky MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- lékařská informatika
- NLK Publikační typ
- ročenky
... Joyce the avant-gardist: the Wake in transition 20 -- 3. ... ... “The voyce crying in the wilderness, rejoice with me”: Brigid Brophy 142 -- 2.5 “A death wish and a sense ... ... of sin\": Ann Quin 148 -- 2.6 “Who’s she when she’s (not) at home”: Christine Brooke-Rose (1964-1975 ... ... Burroughs -- 173 -- 3.2 \"The self who could do more”: William Gaddis 183 -- 3.3 \"That style which deliberately ... ... exhausts its possibilities”: John Barth 189 -- 3.4 \"Never cut when you can paste”: William H. ...
1. elektronické vydání 1 online zdroj (510 stran)
... - H. ... ... Delesie, W. ... ... de Mo es, H. ... ... Flier, W.M. ... ... Miinker, H. Jansen-Dittmer, M. Dahm, R. Schubert, D. Meyer-Ebrecht, W. Hargens, E. Zehn, L. ...
xix, 443 stran : ilustrace, tabulky ; 24 cm
... WAGONER -- 1 ■ Overview, 3 -- CLAES H. ... ... PARK, KING W. TO, ALAN H. FRIEDMAN, and -- FREDERICK A. ... ... WESTFALL, ANN SULLIVAN BAKER, and -- JOHN W. ... ... ROBB -- 201 ■ Optic Neuritis, SHIRLEY H. ... ... WESTFALL and JOHN W. ...
[1st ed.] 5 sv. : il. ; 28 cm
- MeSH
- oční nemoci MeSH
- oftalmologie MeSH
- Konspekt
- Ortopedie. Chirurgie. Oftalmologie
- NLK Obory
- oftalmologie
... -- William E. ... ... Huhta -- 60 Tetralogy of Fallot and Tetralogy of Fallot with -- Pulmonary Atresia 1383 -- William H. ... ... Ettedgui -- 61 Absent Pulmonary Valve Syndrome 1413 -- William W. ... ... Ward Charles E. Mullins -- 64 Transposition of the Great Arteries 1463 -- William H. Neches Sang C. ... ... Feltes John W. ...
Second edition 2 svazky : ilustrace ; 29 cm
... Sverdlov, and Wilson S. ... ... of heart failure / W. ... ... H. Wilson Tang and Gary S. Francis -- Cardiac imaging in heart failure / Martin St. ... ... Maurer, and Michael W. ... ... Mullens, Frederik H. ...
Third edition xxi, 762 stran : ilustrace, grafy ; 29 cm
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- kardiologie
- NLK Publikační typ
- kolektivní monografie
... -- William E. ... ... Huhta -- 60 Tetralogy of Fallot and Tetralogy of Fallot with -- Pulmonary Atresia 1383 -- William H. ... ... Ettedgui -- 61 Absent Pulmonary Valve Syndrome 1413 -- William W. ... ... Ward Charles E. Mullins -- 64 Transposition of the Great Arteries 1463 -- William H. Neches Sang C. ... ... Feltes John W. ...
2nd ed. 1505 s.
... -- William E. ... ... Huhta -- 60 Tetralogy of Fallot and Tetralogy of Fallot with -- Pulmonary Atresia 1383 -- William H. ... ... Ettedgui -- 61 Absent Pulmonary Valve Syndrome 1413 -- William W. ... ... Ward Charles E. Mullins -- 64 Transposition of the Great Arteries 1463 -- William H. Neches Sang C. ... ... Feltes John W. ...
2nd ed. S.1506-2956
