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Blood. 2015 Jan 29;125(5):856-9. doi: 10.1182/blood-2014-09-600874. Epub 2014 Dec 17.

Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.

Author information

1
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
2
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;
3
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;
4
Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece;
5
Department of Informatics, Aristotle University of Thessaloniki, Thessaloniki, Greece;
6
Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom;
7
The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY;
8
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN;
9
Central European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic;
10
Department of Immunology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands;
11
Department of Hematology, Rigshospitalet, Copenhagen, Denmark;
12
Hôpital Pitié-Salpêtrière, Service d'Hématologie Biologique, Paris, France;
13
First Department of Propaedeutic Medicine, University of Athens, Athens, Greece;
14
Hematology Department, Nikea General Hospital, Piraeus, Greece;
15
Molecular Pathology Unit and Haematology Department, Niguarda Cancer Center, Niguarda Ca' Granda Hospital, Milan, Italy;
16
Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden;
17
ImMunoGeneTics (IMGT), Université de Montpellier, Laboratoire d'Informatique Gaspard-Monge, Institut de Génétique Humaine, Montpellier, France;
18
Department of Hematology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands;
19
Hematology Department and University Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France;
20
Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden;
21
Hematology Department and Hematopoietic Cell Transplantation Unit, Georgios Papanicolaou Hospital, Thessaloniki, Greece;
22
Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Italy; Venetian Institute of Molecular Medicine, Padova, Italy;
23
Department of Hemato-Oncology, Belfast City Hospital, Belfast, United Kingdom;
24
Department of Immunology, Mayo Clinic, Rochester, MN; and.
25
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
26
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;

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.

PMID:
25634617
PMCID:
PMC4311230
DOI:
10.1182/blood-2014-09-600874
[Indexed for MEDLINE]
Free PMC Article

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