Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes

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Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors : Shared and Distinct Immunogenetic Features and Clinical Outcomes

Xochelli, Aliki (author): Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,CERTH, Inst Appl Biosci, Thessaloniki, Greece,Center for Research and Technology Hellas

Baliakas, Panagiotis, 1977- (author): Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi,.

Kavakiotis, Ioannis (author): Aristotle Univ Thessaloniki, Dept Informat, Thessaloniki, Greece.,Aristotle University of Thessaloniki

Agathangelidis, Andreas (author): Karolinska Institutet,San Raffaele Scientific Institute,Center for Research and Technology Hellas

Sutton, Lesley Ann (author): Uppsala University,Karolinska Institute,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.

Minga, Eva (author): CERTH, Inst Appl Biosci, Thessaloniki, Greece.,Center for Research and Technology Hellas

Ntoufa, Stavroula (author): CERTH, Inst Appl Biosci, Thessaloniki, Greece.,Center for Research and Technology Hellas

Tausch, Eugen (author): Ulm Univ, Dept Internal Med 3, Ulm, Germany.,University of Ulm

Yan, Xiao-Jie (author): Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA.,Feinstein Institute for Medical Research

Shanafelt, Tait (author): Mayo Clin, Dept Med, Dept Hematol, Rochester, MN USA.,Mayo Clinic Minnesota

Plevova, Karla (author): Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.,Masaryk University

Boudjogra, Myriam (author): Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France.,Paris-Sorbonne University

Rossi, Davide (author): Univ Piemonte Orientale, Dept Translat Med, Dept Haematol, Novara, Italy.,University of Eastern Piedmont

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

Navarro, Alba (author): Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Barcelona, Spain.,University of Barcelona

Sandberg, Yorick (author): Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands.,Erasmus University Medical Center

Vojdeman, Fie Juhl (author): Rigshosp, Dept Haematol, Copenhagen, Denmark.,Copenhagen University Hospital

Scarfo, Lydia (author): IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.,San Raffaele Scientific Institute

Stavroyianni, Niki (author): G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.,George Papanicolaou General Hospital

Sudarikov, Andrey (author): Natl Res Ctr Hematol, Moscow, Russia.,National Research Center for Hematology

Veronese, Silvio (author): Osped Niguarda Ca Granda, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Dept Haematol, Milan, Italy.,Niguarda Hospital

Tzenou, Tatiana (author): Univ Athens, Dept Propaedeut Med 1, Athens, Greece.,National and Kapodistrian University of Athens

Karan-Djurasevic, Teodora (author): Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia.,University of Belgrade

Catherwood, Mark (author): Belfast City Hosp, Dept Haematooncol, Belfast, Antrim, North Ireland.,Belfast City Hospital

Kienle, Dirk (author): Ulm Univ, Dept Internal Med 3, Ulm, Germany.,University of Ulm

Chatzouli, Maria (author): Nikea Gen Hosp, Dept Hematol, Piraeus, Greece.,Nikea General Hospital, Piraeus

Facco, Monica (author): Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy.,University of Padova

Bahlo, Jasmin (author): Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany.;Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany.,University Hospital of Cologne

Pott, Christiane (author): Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany.,University Medical Center Schleswig-Holstein

Pedersen, Lone Bredo (author): Rigshosp, Dept Haematol, Copenhagen, Denmark.,Copenhagen University Hospital

Mansouri, Larry (author): Uppsala University,Karolinska Institute,Karolinska Institutet,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.

Smedby, Karin E. (author): Karolinska Institute,Karolinska Institutet

Chu, Charles C. (author): Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA.,Feinstein Institute for Medical Research

Giudicelli, Veronique (author): Univ Montpellier, CNRS, UPR 1142, IMGT,LIGM,IGH, Montpellier, France.,Institut de Génétique Humaine

Lefranc, Marie-Paule (author): Univ Montpellier, CNRS, UPR 1142, IMGT,LIGM,IGH, Montpellier, France.,Institut de Génétique Humaine

Panagiotidis, Panagiotis (author): Univ Athens, Dept Propaedeut Med 1, Athens, Greece.,National and Kapodistrian University of Athens

Juliusson, Gunnar (author): 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,Skåne University Hospital

Anagnostopoulos, Achilles (author): G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.,George Papanicolaou General Hospital

Vlahavas, Ioannis (author): Aristotle Univ Thessaloniki, Dept Informat, Thessaloniki, Greece.,Aristotle University of Thessaloniki

Antic, Darko (author): Ctr Clin, Clin Hematol, Belgrade, Serbia.;Univ Belgrade, Fac Med, Belgrade, Serbia.,University of Belgrade

Trentin, Livio (author): Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy.,University of Padova

Montillo, Marco (author): Osped Niguarda Ca Granda, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Dept Haematol, Milan, Italy.,Niguarda Hospital

Niemann, Carsten (author): Rigshosp, Dept Haematol, Copenhagen, Denmark.,Copenhagen University Hospital

Doehner, Hartmut (author): Ulm Univ, Dept Internal Med 3, Ulm, Germany.,University of Ulm

Langerak, Anton W. (author): Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands.,Erasmus University Medical Center

Pospisilova, Sarka (author): Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.,Masaryk University

Hallek, Michael (author): Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany.;Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany.,University Hospital of Cologne

Campo, Elias (author): Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Barcelona, Spain.,University of Barcelona

Chiorazzi, Nicholas (author): Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA.,Feinstein Institute for Medical Research

Maglaveras, Nikos (author): Aristotle Univ Thessaloniki, Lab Med Informat, Thessaloniki, Greece.,Aristotle University of Thessaloniki

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

Gaidano, Gianluca (author): Univ Piemonte Orientale, Dept Translat Med, Dept Haematol, Novara, Italy.,University of Eastern Piedmont

Jelinek, Diane F. (author): Mayo Clin, Dept Immunol, Rochester, MN USA.,Mayo Clinic Minnesota

Stilgenbauer, Stephan (author): Ulm Univ, Dept Internal Med 3, Ulm, Germany.,University of Ulm

Chouvarda, Ioanna (author): Aristotle Univ Thessaloniki, Lab Med Informat, Thessaloniki, Greece.,Aristotle University of Thessaloniki

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

Belessi, Chrysoula (author): Nikea Gen Hosp, Dept Hematol, Piraeus, Greece.,Nikea General Hospital, Piraeus

Davi, Frederic (author): Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France.,Paris-Sorbonne University

Hadzidimitriou, Anastasia (author): Uppsala University,Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,CERTH, Inst Appl Biosci, Thessaloniki, Greece.,Center for Research and Technology Hellas

Rosenquist, Richard (author): Uppsala University,Karolinska Institute,Karolinska Institutet,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi,Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.

Ghia, Paolo (author): IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS Ist Sci San Raffaele, Milan, Italy.,San Raffaele Scientific Institute,Vita-Salute San Raffaele University

Stamatopoulos, Kostas (author): Uppsala University,Uppsala universitet,Experimentell och klinisk onkologi,CERTH, Inst Appl Biosci, Thessaloniki, Greece ;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.,Center for Research and Technology Hellas,George Papanicolaou General Hospital

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(creator_code:org_t)

2017
2017
English.
In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 23:17, s. 5292-5301

Related links:: http://dx.doi.org/10...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; http://kipublication...; https://lup.lub.lu.s...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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 < 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.

Subject headings

NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

B-cell receptors
gene mutational status
antigen receptors
CD38 expression
genomic aberrations
sequence-analysis
I-antigen
immunoglobulin
antibodies
dna
LEUKEMIA
IGHV4-34 Receptors
Clinical Outcomes

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ref (subject category)
art (subject category)

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By the author/editor: Xochelli, Aliki; Baliakas, Panagi ...; Kavakiotis, Ioan ...; Agathangelidis, ...; Sutton, Lesley A ...; Minga, Eva; show more...; Ntoufa, Stavroul ...; Tausch, Eugen; Yan, Xiao-Jie; Shanafelt, Tait; Plevova, Karla; Boudjogra, Myria ...; Rossi, Davide; Davis, Zadie; Navarro, Alba; Sandberg, Yorick; Vojdeman, Fie Ju ...; Scarfo, Lydia; Stavroyianni, Ni ...; Sudarikov, Andre ...; Veronese, Silvio; Tzenou, Tatiana; Karan-Djurasevic ...; Catherwood, Mark; Kienle, Dirk; Chatzouli, Maria; Facco, Monica; Bahlo, Jasmin; Pott, Christiane; Pedersen, Lone B ...; Mansouri, Larry; Smedby, Karin E.; Chu, Charles C.; Giudicelli, Vero ...; Lefranc, Marie-P ...; Panagiotidis, Pa ...; Juliusson, Gunna ...; Anagnostopoulos, ...; Vlahavas, Ioanni ...; Antic, Darko; Trentin, Livio; Montillo, Marco; Niemann, Carsten; Doehner, Hartmut; Langerak, Anton ...; Pospisilova, Sar ...; Hallek, Michael; Campo, Elias; Chiorazzi, Nicho ...; Maglaveras, Niko ...; Oscier, David; Gaidano, Gianluc ...; Jelinek, Diane F ...; Stilgenbauer, St ...; Chouvarda, Ioann ...; Darzentas, Nikos; Belessi, Chrysou ...; Davi, Frederic; Hadzidimitriou, ...; Rosenquist, Rich ...; Ghia, Paolo; Stamatopoulos, K ...; show less...

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Genetics

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

Articles in the publication: Clinical Cancer ...

By the university: Uppsala University; Karolinska Institutet; Lund University

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