title: Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.
abstract: An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.
authors: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
authors: Panagiotis
authors: P
authors: Baliakas
authors: Università Vita-Salute San Raffaele, Milan, Italy; Division of Molecular Oncology and Department of Onco-Hematology, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy;
authors: Andreas
authors: A
authors: Agathangelidis
authors: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece;
authors: Anastasia
authors: A
authors: Hadzidimitriou
authors: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
authors: Lesley-Ann
authors: LA
authors: Sutton
authors: Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece;
authors: Eva
authors: E
authors: Minga
authors: Department of Informatics, Aristotle University of Thessaloniki, Thessaloniki, Greece;
authors: Athina
authors: A
authors: Tsanousa
authors: Università Vita-Salute San Raffaele, Milan, Italy; Division of Molecular Oncology and Department of Onco-Hematology, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy;
authors: Lydia
authors: L
authors: Scarfò
authors: Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom;
authors: Zadie
authors: Z
authors: Davis
authors: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY;
authors: Xiao-Jie
authors: XJ
authors: Yan
authors: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN;
authors: Tait
authors: T
authors: Shanafelt
authors: Central European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic;
authors: Karla
authors: K
authors: Plevova
authors: Department of Immunology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands;
authors: Yorick
authors: Y
authors: Sandberg
authors: Department of Hematology, Rigshospitalet, Copenhagen, Denmark;
authors: Fie Juhl
authors: FJ
authors: Vojdeman
authors: Hôpital Pitié-Salpêtrière, Service d'Hématologie Biologique, Paris, France;
authors: Myriam
authors: M
authors: Boudjogra
authors: First Department of Propaedeutic Medicine, University of Athens, Athens, Greece;
authors: Tatiana
authors: T
authors: Tzenou
authors: Hematology Department, Nikea General Hospital, Piraeus, Greece;
authors: Maria
authors: M
authors: Chatzouli
authors: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY;
authors: Charles C
authors: CC
authors: Chu
authors: Molecular Pathology Unit and Haematology Department, Niguarda Cancer Center, Niguarda Ca' Granda Hospital, Milan, Italy;
authors: Silvio
authors: S
authors: Veronese
authors: Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom;
authors: Anne
authors: A
authors: Gardiner
authors: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
authors: Larry
authors: L
authors: Mansouri
authors: Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden;
authors: Karin E
authors: KE
authors: Smedby
authors: Department of Hematology, Rigshospitalet, Copenhagen, Denmark;
authors: Lone Bredo
authors: LB
authors: Pedersen
authors: ImMunoGeneTics (IMGT), Université de Montpellier, Laboratoire d'Informatique Gaspard-Monge, Institut de Génétique Humaine, Montpellier, France;
authors: Denis
authors: D
authors: Moreno
authors: Department of Hematology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands;
authors: Kirsten
authors: K
authors: Van Lom
authors: ImMunoGeneTics (IMGT), Université de Montpellier, Laboratoire d'Informatique Gaspard-Monge, Institut de Génétique Humaine, Montpellier, France;
authors: Véronique
authors: V
authors: Giudicelli
authors: Central European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic;
authors: Hana Skuhrova
authors: HS
authors: Francova
authors: Hematology Department and University Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France;
authors: Florence
authors: F
authors: Nguyen-Khac
authors: First Department of Propaedeutic Medicine, University of Athens, Athens, Greece;
authors: Panagiotis
authors: P
authors: Panagiotidis
authors: Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden;
authors: Gunnar
authors: G
authors: Juliusson
authors: Department of Informatics, Aristotle University of Thessaloniki, Thessaloniki, Greece;
authors: Lefteris
authors: L
authors: Angelis
authors: Hematology Department and Hematopoietic Cell Transplantation Unit, Georgios Papanicolaou Hospital, Thessaloniki, Greece;
authors: Achilles
authors: A
authors: Anagnostopoulos
authors: ImMunoGeneTics (IMGT), Université de Montpellier, Laboratoire d'Informatique Gaspard-Monge, Institut de Génétique Humaine, Montpellier, France;
authors: Marie-Paule
authors: MP
authors: Lefranc
authors: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Italy; Venetian Institute of Molecular Medicine, Padova, Italy;
authors: Monica
authors: M
authors: Facco
authors: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Italy; Venetian Institute of Molecular Medicine, Padova, Italy;
authors: Livio
authors: L
authors: Trentin
authors: Department of Hemato-Oncology, Belfast City Hospital, Belfast, United Kingdom;
authors: Mark
authors: M
authors: Catherwood
authors: Molecular Pathology Unit and Haematology Department, Niguarda Cancer Center, Niguarda Ca' Granda Hospital, Milan, Italy;
authors: Marco
authors: M
authors: Montillo
authors: Department of Hematology, Rigshospitalet, Copenhagen, Denmark;
authors: Christian H
authors: CH
authors: Geisler
authors: Department of Immunology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands;
authors: Anton W
authors: AW
authors: Langerak
authors: Central European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic;
authors: Sarka
authors: S
authors: Pospisilova
authors: The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY;
authors: Nicholas
authors: N
authors: Chiorazzi
authors: Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom;
authors: David
authors: D
authors: Oscier
authors: Department of Immunology, Mayo Clinic, Rochester, MN; and.
authors: Diane F
authors: DF
authors: Jelinek
authors: Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors: Nikos
authors: N
authors: Darzentas
authors: Hematology Department, Nikea General Hospital, Piraeus, Greece;
authors: Chrysoula
authors: C
authors: Belessi
authors: Hematology Department and University Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France;
authors: Frederic
authors: F
authors: Davi
authors: Università Vita-Salute San Raffaele, Milan, Italy; Division of Molecular Oncology and Department of Onco-Hematology, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy;
authors: Paolo
authors: P
authors: Ghia
authors: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
authors: Richard
authors: R
authors: Rosenquist
authors: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece; Hematology Department and Hematopoietic Cell Transplantation Unit, Georgios Papanicolaou Hospital, Thessaloniki, Greece;
authors: Kostas
authors: K
authors: Stamatopoulos
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000276:immunology*; D018740:Genetic Heterogeneity; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D027041:Somatic Hypermutation, Immunoglobulin; D016019:Survival Analysis; D061665:Time-to-Treatment; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007143:Immunoglobulin Heavy Chains
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