Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study

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Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study

Baliakas, Panagiotis (författare): Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.

Hadzidimitriou, Anastasia (författare): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,CERTH, Inst Appl Biosci, Thessaloniki, Greece.

Sutton, Lesley-Ann (författare): Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab

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Minga, Eva (författare): CERTH, Inst Appl Biosci, Thessaloniki, Greece.

Agathangelidis, Andreas (författare): Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Div Mol Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, I-20132 Milan, Italy.

Nichelatti, Michele (författare): Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy.

Tsanousa, Athina (författare): Aristotle Univ Thessaloniki, Dept Informat, GR-54006 Thessaloniki, Greece.

Scarfo, Lydia (författare): Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Div Mol Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, I-20132 Milan, Italy.

Davis, Zadie (författare): Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England.

Yan, Xiao-Jie (författare): North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA.

Shanafelt, Tait (författare): Mayo Clin, Div Hematol, Dept Med, Rochester, MN USA.

Plevova, Karla (författare): Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic.

Sandberg, Yorick (författare): Erasmus MC, Univ Med Ctr, Dept Immunol, Rotterdam, Netherlands.

Vojdeman, Fie Juhl (författare): Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark.

Boudjogra, Myriam (författare): Hop La Pitie Salpetriere, Serv Hematol Biol, Paris, France.

Tzenou, Tatiana (författare): Univ Athens, Dept Propaedeut Med, Athens, Greece.

Chatzouli, Maria (författare): Nikea Gen Hosp, Dept Hematol, Piraeus, Greece.

Chu, Charles C. (författare): North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA.

Veronese, Silvio (författare): Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy.

Gardiner, Anne (författare): Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England.

Mansouri, Larry (författare): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi,Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden.

Smedby, Karin E. (författare): Karolinska Institutet

Pedersen, Lone Bredo (författare): Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark.

van Lom, Kirsten (författare): Erasmus MC, Univ Med Ctr, Dept Hematol, Rotterdam, Netherlands.

Giudicelli, Veronique (författare): Univ Montpellier, IMGT Int ImMunoGeneT Informat Syst, LIGM, Inst Genet Humaine, F-34059 Montpellier, France.

Francova, Hana Skuhrova (författare): Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic.

Nguyen-Khac, Florence (författare): Hop La Pitie Salpetriere, Serv Hematol Biol, Paris, France.

Panagiotidis, Panagiotis (författare): Univ Athens, Dept Propaedeut Med, Athens, Greece.

Juliusson, Gunnar (författare): Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Lund Univ & Hosp, Dept Hematol, Lund Stem Cell Ctr, Lund, Sweden.

Angelis, Lefteris (författare): Aristotle Univ Thessaloniki, Dept Informat, GR-54006 Thessaloniki, Greece.

Anagnostopoulos, Achilles (författare): G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.

Lefranc, Marie-Paule (författare): Univ Montpellier, IMGT Int ImMunoGeneT Informat Syst, LIGM, Inst Genet Humaine, F-34059 Montpellier, France.

Facco, Monica (författare): Univ Padua, Sch Med, Dept Med, Hematol & Clin Immunol Branch, I-35100 Padua, Italy.;Venetian Inst Mol Med, Padua, Italy.

Trentin, Livio (författare): Univ Padua, Sch Med, Dept Med, Hematol & Clin Immunol Branch, I-35100 Padua, Italy.;Venetian Inst Mol Med, Padua, Italy.

Catherwood, Mark (författare): Belfast City Hosp, Dept Haematooncol, Belfast BT9 7AD, Antrim, North Ireland.

Montillo, Marco (författare): Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy.

Geisler, Christian H. (författare): Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark.

Langerak, Anton W. (författare): Erasmus MC, Univ Med Ctr, Dept Immunol, Rotterdam, Netherlands.

Pospisilova, Sarka (författare): Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic.

Chiorazzi, Nicholas (författare): North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA.

Oscier, David (författare): Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England.

Jelinek, Diane F. (författare): Mayo Clin, Dept Immunol, Dept Med, Rochester, MN USA.

Darzentas, Nikos (författare): Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.

Belessi, Chrysoula (författare): Nikea Gen Hosp, Dept Hematol, Piraeus, Greece.

Davi, Frederic (författare): Hop La Pitie Salpetriere, Serv Hematol Biol, Paris, France.

Rosenquist Barndell, Richard (författare): Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab

Ghia, Paolo (författare): Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Div Mol Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, I-20132 Milan, Italy.

Stamatopoulos, Kostas (författare): Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi,G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece.

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2014
2014
Engelska.
Ingår i: The Lancet Haematology. - 2352-3026. ; 1:2, s. 74-84

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Tidskriftsartikel (refereegranskat)

Abstract Ämnesord

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Background About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptor immunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggests that B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never been explored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn. Methods For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogenetic data were available. These patients were followed up in 15 academic institutions throughout Europe (in Czech Republic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collected between June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptor immunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressing unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome of our analysis was time to first treatment, defined as the time between diagnosis and date of first treatment. Findings 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 major subsets. Stereotyped subsets showed significant differences in terms of age, sex, disease burden at diagnosis, CD38 expression, and cytogenetic aberrations of prognostic significance. Patients within a specific subset generally followed the same clinical course, whereas patients in different stereotyped subsets-despite having the same immunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status-showed substantially different times to first treatment. By integrating B-cell receptor immunoglobulin stereotypy (for subsets 1, 2, and 4) into the well established Dohner cytogenetic prognostic model, we showed these, which collectively account for around 7% of all cases of CLL and represent both U-CLL and M-CLL, constituted separate clinical entities, ranging from very indolent (subset 4) to aggressive disease (subsets 1 and 2). Interpretation The molecular classification of chronic lymphocytic leukaemia based on B-cell receptor immunoglobulin stereotypy improves the Dohner hierarchical model and refines prognostication beyond immunoglobulin mutational status, with potential implications for clinical decision making, especially within prospective clinical trials.

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Av författaren/redakt...: Baliakas, Panagi ...; Hadzidimitriou, ...; Sutton, Lesley-A ...; Minga, Eva; Agathangelidis, ...; Nichelatti, Mich ...; visa fler...; Tsanousa, Athina; Scarfo, Lydia; Davis, Zadie; Yan, Xiao-Jie; Shanafelt, Tait; Plevova, Karla; Sandberg, Yorick; Vojdeman, Fie Ju ...; Boudjogra, Myria ...; Tzenou, Tatiana; Chatzouli, Maria; Chu, Charles C.; Veronese, Silvio; Gardiner, Anne; Mansouri, Larry; Smedby, Karin E.; Pedersen, Lone B ...; van Lom, Kirsten; Giudicelli, Vero ...; Francova, Hana S ...; Nguyen-Khac, Flo ...; Panagiotidis, Pa ...; Juliusson, Gunna ...; Angelis, Lefteri ...; Anagnostopoulos, ...; Lefranc, Marie-P ...; Facco, Monica; Trentin, Livio; Catherwood, Mark; Montillo, Marco; Geisler, Christi ...; Langerak, Anton ...; Pospisilova, Sar ...; Chiorazzi, Nicho ...; Oscier, David; Jelinek, Diane F ...; Darzentas, Nikos; Belessi, Chrysou ...; Davi, Frederic; Rosenquist Barnd ...; Ghia, Paolo; Stamatopoulos, K ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Hematologi

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

Artiklar i publikationen: The Lancet Haema ...

Av lärosätet: Lunds universitet; Uppsala universitet; Karolinska Institutet

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Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study

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