Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes
Samo za registrovane korisnike
2017
Autori
Xochelli, AlikiBaliakas, Panagiotis
Kavakiotis, Ioannis
Agathangelidis, Andreas
Sutton, Lesley-Ann
Minga, Eva
Ntoufa, Stavroula
Tausch, Eugen
Yan, Xiao-Jie
Shanafelt, Tait
Plevova, Karla
Boudjogra, Myriam
Rossi, Davide
Davis, Zadie
Navarro, Alba
Sandberg, Yorick
Vojdeman, Fie Juhl
Scarfo, Lydia
Stavroyianni, Niki
Sudarikov, Andrey
Veronese, Silvio
Tzenou, Tatiana
Karan-Đurašević, Teodora
Catherwood, Mark
Kienle, Dirk
Chatzouli, Maria
Facco, Monica
Bahlo, Jasmin
Pott, Christiane
Pedersen, Lone Bredo
Mansouri, Larry
Smedby, Karin E.
Chu, Charles C.
Giudicelli, Veronique
Lefranc, Marie-Paule
Panagiotidis, Panagiotis
Juliusson, Gunnar
Anagnostopoulos, Achilles
Vlahavas, Ioannis
Antić, Darko
Trentin, Livio
Montillo, Marco
Niemann, Carsten
Doehner, Hartmut
Langerak, Anton W.
Pospisilova, Sarka
Hallek, Michael
Campo, Elias
Chiorazzi, Nicholas
Maglaveras, Nikos
Oscier, David
Gaidano, Gianluca
Jelinek, Diane F.
Stilgenbauer, Stephan
Chouvarda, Ioanna
Darzentas, Nikos
Belessi, Chrysoula
Davi, Frederic
Hadzidimitriou, Anastasia
Rosenquist, Richard
Ghia, Paolo
Stamatopoulos, Kostas
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter co...ncerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P lt 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management.
Izvor:
Clinical Cancer Research, 2017, 23, 17, 5292-5301Izdavač:
- Amer Assoc Cancer Research, Philadelphia
Finansiranje / projekti:
- H "AEGLE, An analytics framework for integrated and personalized healthcare services in Europe", by the EU
- H project "MEDGENET, Medical Genomics and Epigenomics Network" by the EU [692298]
- Swedish Cancer Society
- Swedish Research Council
- Uppsala University
- Uppsala University Hospital
- Lion's Cancer Research Foundation
- Selander's Foundation, Uppsala
- Associazione Italiana per la Ricerca sul Cancro, Milano, Italy [IG15189, 9965, 10007]
- Ricerca Finalizzata [RF-2010-2318823]
- Ministero della Salute, Roma, Italy [RF-2011-02349712]
- MEYS CZ project NPUII - CEITEC [LQ1601]
- Novo Nordisk Fonden [NNF16OC0019302] Funding Source: researchfish
- The Danish Cancer Society [R130-A8217] Funding Source: researchfish
Napomena:
- This is the peer-reviewed version of the article: Xochelli, A., Baliakas, P., Kavakiotis, I., Agathangelidis, A., Sutton, L.-A., Minga, E., Ntoufa, S., Tausch, E., Yan, X.-J., Shanafelt, T., Plevova, K., Boudjogra, M., Rossi, D., Davis, Z., Navarro, A., Sandberg, Y., Vojdeman, F. J., Scarfo, L., Stavroyianni, N., … Stamatopoulos, K. (2017). Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinica Outcomes. Clinical Cancer Research, 23(17), 5292–5301. https://imagine.imgge.bg.ac.rs/handle/123456789/1611
Povezane informacije:
- Druga verzija
https://doi.org/10.1158/1078-0432.CCR-16-3100 - Druga verzija
https://imagine.imgge.bg.ac.rs/handle/123456789/1611
DOI: 10.1158/1078-0432.CCR-16-3100
ISSN: 1078-0432
PubMed: 28536306
WoS: 000409037300034
Scopus: 2-s2.0-85029456308
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Xochelli, Aliki AU - Baliakas, Panagiotis AU - Kavakiotis, Ioannis AU - Agathangelidis, Andreas AU - Sutton, Lesley-Ann AU - Minga, Eva AU - Ntoufa, Stavroula AU - Tausch, Eugen AU - Yan, Xiao-Jie AU - Shanafelt, Tait AU - Plevova, Karla AU - Boudjogra, Myriam AU - Rossi, Davide AU - Davis, Zadie AU - Navarro, Alba AU - Sandberg, Yorick AU - Vojdeman, Fie Juhl AU - Scarfo, Lydia AU - Stavroyianni, Niki AU - Sudarikov, Andrey AU - Veronese, Silvio AU - Tzenou, Tatiana AU - Karan-Đurašević, Teodora AU - Catherwood, Mark AU - Kienle, Dirk AU - Chatzouli, Maria AU - Facco, Monica AU - Bahlo, Jasmin AU - Pott, Christiane AU - Pedersen, Lone Bredo AU - Mansouri, Larry AU - Smedby, Karin E. AU - Chu, Charles C. AU - Giudicelli, Veronique AU - Lefranc, Marie-Paule AU - Panagiotidis, Panagiotis AU - Juliusson, Gunnar AU - Anagnostopoulos, Achilles AU - Vlahavas, Ioannis AU - Antić, Darko AU - Trentin, Livio AU - Montillo, Marco AU - Niemann, Carsten AU - Doehner, Hartmut AU - Langerak, Anton W. AU - Pospisilova, Sarka AU - Hallek, Michael AU - Campo, Elias AU - Chiorazzi, Nicholas AU - Maglaveras, Nikos AU - Oscier, David AU - Gaidano, Gianluca AU - Jelinek, Diane F. AU - Stilgenbauer, Stephan AU - Chouvarda, Ioanna AU - Darzentas, Nikos AU - Belessi, Chrysoula AU - Davi, Frederic AU - Hadzidimitriou, Anastasia AU - Rosenquist, Richard AU - Ghia, Paolo AU - Stamatopoulos, Kostas PY - 2017 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1017 AB - Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P lt 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. PB - Amer Assoc Cancer Research, Philadelphia T2 - Clinical Cancer Research T1 - Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes EP - 5301 IS - 17 SP - 5292 VL - 23 DO - 10.1158/1078-0432.CCR-16-3100 ER -
@article{ author = "Xochelli, Aliki and Baliakas, Panagiotis and Kavakiotis, Ioannis and Agathangelidis, Andreas and Sutton, Lesley-Ann and Minga, Eva and Ntoufa, Stavroula and Tausch, Eugen and Yan, Xiao-Jie and Shanafelt, Tait and Plevova, Karla and Boudjogra, Myriam and Rossi, Davide and Davis, Zadie and Navarro, Alba and Sandberg, Yorick and Vojdeman, Fie Juhl and Scarfo, Lydia and Stavroyianni, Niki and Sudarikov, Andrey and Veronese, Silvio and Tzenou, Tatiana and Karan-Đurašević, Teodora and Catherwood, Mark and Kienle, Dirk and Chatzouli, Maria and Facco, Monica and Bahlo, Jasmin and Pott, Christiane and Pedersen, Lone Bredo and Mansouri, Larry and Smedby, Karin E. and Chu, Charles C. and Giudicelli, Veronique and Lefranc, Marie-Paule and Panagiotidis, Panagiotis and Juliusson, Gunnar and Anagnostopoulos, Achilles and Vlahavas, Ioannis and Antić, Darko and Trentin, Livio and Montillo, Marco and Niemann, Carsten and Doehner, Hartmut and Langerak, Anton W. and Pospisilova, Sarka and Hallek, Michael and Campo, Elias and Chiorazzi, Nicholas and Maglaveras, Nikos and Oscier, David and Gaidano, Gianluca and Jelinek, Diane F. and Stilgenbauer, Stephan and Chouvarda, Ioanna and Darzentas, Nikos and Belessi, Chrysoula and Davi, Frederic and Hadzidimitriou, Anastasia and Rosenquist, Richard and Ghia, Paolo and Stamatopoulos, Kostas", year = "2017", abstract = "Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P lt 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management.", publisher = "Amer Assoc Cancer Research, Philadelphia", journal = "Clinical Cancer Research", title = "Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes", pages = "5301-5292", number = "17", volume = "23", doi = "10.1158/1078-0432.CCR-16-3100" }
Xochelli, A., Baliakas, P., Kavakiotis, I., Agathangelidis, A., Sutton, L., Minga, E., Ntoufa, S., Tausch, E., Yan, X., Shanafelt, T., Plevova, K., Boudjogra, M., Rossi, D., Davis, Z., Navarro, A., Sandberg, Y., Vojdeman, F. J., Scarfo, L., Stavroyianni, N., Sudarikov, A., Veronese, S., Tzenou, T., Karan-Đurašević, T., Catherwood, M., Kienle, D., Chatzouli, M., Facco, M., Bahlo, J., Pott, C., Pedersen, L. B., Mansouri, L., Smedby, K. E., Chu, C. C., Giudicelli, V., Lefranc, M., Panagiotidis, P., Juliusson, G., Anagnostopoulos, A., Vlahavas, I., Antić, D., Trentin, L., Montillo, M., Niemann, C., Doehner, H., Langerak, A. W., Pospisilova, S., Hallek, M., Campo, E., Chiorazzi, N., Maglaveras, N., Oscier, D., Gaidano, G., Jelinek, D. F., Stilgenbauer, S., Chouvarda, I., Darzentas, N., Belessi, C., Davi, F., Hadzidimitriou, A., Rosenquist, R., Ghia, P.,& Stamatopoulos, K.. (2017). Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes. in Clinical Cancer Research Amer Assoc Cancer Research, Philadelphia., 23(17), 5292-5301. https://doi.org/10.1158/1078-0432.CCR-16-3100
Xochelli A, Baliakas P, Kavakiotis I, Agathangelidis A, Sutton L, Minga E, Ntoufa S, Tausch E, Yan X, Shanafelt T, Plevova K, Boudjogra M, Rossi D, Davis Z, Navarro A, Sandberg Y, Vojdeman FJ, Scarfo L, Stavroyianni N, Sudarikov A, Veronese S, Tzenou T, Karan-Đurašević T, Catherwood M, Kienle D, Chatzouli M, Facco M, Bahlo J, Pott C, Pedersen LB, Mansouri L, Smedby KE, Chu CC, Giudicelli V, Lefranc M, Panagiotidis P, Juliusson G, Anagnostopoulos A, Vlahavas I, Antić D, Trentin L, Montillo M, Niemann C, Doehner H, Langerak AW, Pospisilova S, Hallek M, Campo E, Chiorazzi N, Maglaveras N, Oscier D, Gaidano G, Jelinek DF, Stilgenbauer S, Chouvarda I, Darzentas N, Belessi C, Davi F, Hadzidimitriou A, Rosenquist R, Ghia P, Stamatopoulos K. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes. in Clinical Cancer Research. 2017;23(17):5292-5301. doi:10.1158/1078-0432.CCR-16-3100 .
Xochelli, Aliki, Baliakas, Panagiotis, Kavakiotis, Ioannis, Agathangelidis, Andreas, Sutton, Lesley-Ann, Minga, Eva, Ntoufa, Stavroula, Tausch, Eugen, Yan, Xiao-Jie, Shanafelt, Tait, Plevova, Karla, Boudjogra, Myriam, Rossi, Davide, Davis, Zadie, Navarro, Alba, Sandberg, Yorick, Vojdeman, Fie Juhl, Scarfo, Lydia, Stavroyianni, Niki, Sudarikov, Andrey, Veronese, Silvio, Tzenou, Tatiana, Karan-Đurašević, Teodora, Catherwood, Mark, Kienle, Dirk, Chatzouli, Maria, Facco, Monica, Bahlo, Jasmin, Pott, Christiane, Pedersen, Lone Bredo, Mansouri, Larry, Smedby, Karin E., Chu, Charles C., Giudicelli, Veronique, Lefranc, Marie-Paule, Panagiotidis, Panagiotis, Juliusson, Gunnar, Anagnostopoulos, Achilles, Vlahavas, Ioannis, Antić, Darko, Trentin, Livio, Montillo, Marco, Niemann, Carsten, Doehner, Hartmut, Langerak, Anton W., Pospisilova, Sarka, Hallek, Michael, Campo, Elias, Chiorazzi, Nicholas, Maglaveras, Nikos, Oscier, David, Gaidano, Gianluca, Jelinek, Diane F., Stilgenbauer, Stephan, Chouvarda, Ioanna, Darzentas, Nikos, Belessi, Chrysoula, Davi, Frederic, Hadzidimitriou, Anastasia, Rosenquist, Richard, Ghia, Paolo, Stamatopoulos, Kostas, "Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes" in Clinical Cancer Research, 23, no. 17 (2017):5292-5301, https://doi.org/10.1158/1078-0432.CCR-16-3100 . .