General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL

被引:114
作者
Fazi, Claudia [2 ]
Scarfo, Lydia [1 ,2 ,3 ]
Pecciarini, Lorenza [4 ]
Cottini, Francesca [2 ,5 ]
Dagklis, Antonis [2 ]
Janus, Agnieszka [2 ]
Talarico, Anna [4 ]
Scielzo, Cristina [6 ]
Sala, Cinzia [7 ]
Toniolo, Daniela [7 ]
Caligaris-Cappio, Federico [1 ,5 ,6 ,8 ]
Ghia, Paolo [1 ,2 ,5 ,8 ]
机构
[1] Ist Sci San Raffaele, Lymphoma Unit, Dept Oncohematol, I-20132 Milan, Italy
[2] Ist Sci San Raffaele, Lab Cell Neoplasia B, Div Mol Oncol, I-20132 Milan, Italy
[3] Univ Ferrara, Inst Hematol, I-44100 Ferrara, Italy
[4] Ist Sci San Raffaele, Pathol Unit, I-20132 Milan, Italy
[5] Univ Vita Salute San Raffaele, Milan, Italy
[6] Ist Sci San Raffaele, Lab Lymphoid Malignancies, Div Mol Oncol, I-20132 Milan, Italy
[7] Ist Sci San Raffaele, Unit Genet Common Disorder, Div Genet & Cell Biol, I-20132 Milan, Italy
[8] Ist Sci San Raffaele, MAGIC Microenvironm & Genes Canc Blood Interdivis, I-20132 Milan, Italy
关键词
B-CELL LYMPHOCYTOSIS; PERIPHERAL-BLOOD; IGV(H) STATUS; LEUKEMIA; AGE; BIOLOGY; INDIVIDUALS; ABERRATIONS; EXPANSIONS; REPERTOIRE;
D O I
10.1182/blood-2011-05-357251
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Monoclonal B-cell lymphocytosis (MBL) is classified as chronic lymphocytic leukemia (CLL)-like, atypical CLL, and CD5(-) MBL. The number of B cells per microliter divides CLL-like MBL into MBL associated with lymphocytosis (usually detected in a clinical setting) and low-count MBL detected in the general population (usually identified during population screening). After a median follow-up of 34 months we reevaluated 76 low-count MBLs with 5-color flow cytometry: 90% of CLL-like MBL but only 44.4% atypical CLL and 66.7% CD5(-) MBL persisted over time. Population-screening CLL-like MBL had no relevant cell count change, and none developed an overt leukemia. In 50% of the cases FISH showed CLL-related chromosomal abnormalities, including monoallelic or biallelic 13q deletions (43.8%), trisomy 12 (1 case), and 17p deletions (2 cases). The analysis of the T-cell receptor beta (TRBV) chains repertoire showed the presence of monoclonal T-cell clones, especially among CD4(high)CD8(low), CD8(high)CD4(low) T cells. TRBV2 and TRBV8 were the most frequently expressed genes. This study indicates that (1) the risk of progression into CLL for lowcount population-screening CLL-like MBL is exceedingly rare and definitely lower than that of clinical MBL and (2) chromosomal abnormalities occur early in the natural history and are possibly associated with the appearance of the typical phenotype. (Blood. 2011; 118(25): 6618-6625)
引用
收藏
页码:6618 / 6625
页数:8
相关论文
共 30 条
[1]   A subset of Binet stage A CLL patients with TP53 abnormalities and mutated IGHV genes have stable disease [J].
Best, O. G. ;
Gardiner, A. C. ;
Davis, Z. A. ;
Tracy, I. ;
Ibbotson, R. E. ;
Majid, A. ;
Dyer, M. J. S. ;
Oscier, D. G. .
LEUKEMIA, 2009, 23 (01) :212-214
[2]   Age-related persistent clonal expansions of CD28- cells:: Phenotypic and molecular TCR analysis reveals both CD4+ and CD4+ CD8+ cells with identical CDR3 sequences [J].
Colombatti, A ;
Doliana, R ;
Schiappacassi, M ;
Argentini, C ;
Tonutti, E ;
Feruglio, C ;
Sala, P .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1998, 89 (01) :61-70
[3]   The immunoglobulin gene repertoire of low-count chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis is different from CLL: diagnostic implications for clinical monitoring [J].
Dagklis, Antonis ;
Fazi, Claudia ;
Sala, Cinzia ;
Cantarelli, Valeria ;
Scielzo, Cristina ;
Massacane, Roberto ;
Toniolo, Daniela ;
Caligaris-Cappio, Federico ;
Stamatopoulos, Kostas ;
Ghia, Paolo .
BLOOD, 2009, 114 (01) :26-32
[4]   Monoclonal B-cell lymphocytosis (MBL) in CLL families: substantial increase in relative risk for young adults [J].
de Tute, R ;
Yuille, M ;
Catovsky, D ;
Houlston, RS ;
Hillmen, P ;
Rawstron, AC .
LEUKEMIA, 2006, 20 (04) :728-729
[5]   Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients:: a study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression [J].
Dicker, Frank ;
Schnittger, Susanne ;
Haferlach, Torsten ;
Kern, Wolfgang ;
Schoch, Claudia .
BLOOD, 2006, 108 (09) :3152-3160
[6]   Genomic aberrations and survival in chronic lymphocytic leukemia. [J].
Döhner, H ;
Stilgenbauer, S ;
Benner, A ;
Leupolt, E ;
Kröber, A ;
Bullinger, L ;
Döhner, K ;
Bentz, M ;
Lichter, P .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (26) :1910-1916
[7]   Monoclonal B Cell Lymphocytosis in Hepatitis C Virus Infected Individuals [J].
Fazi, Claudia ;
Dagklis, Antonis ;
Cottini, Francesca ;
Scarfo, Lydia ;
Bertilaccio, Maria Teresa Sabrina ;
Finazzi, Renato ;
Memoli, Massimo ;
Ghia, Paolo .
CYTOMETRY PART B-CLINICAL CYTOMETRY, 2010, 78B :S61-S68
[8]   Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly [J].
Ghia, P ;
Prato, G ;
Scielzo, C ;
Stella, S ;
Geuna, M ;
Guida, G ;
Caligaris-Cappio, F .
BLOOD, 2004, 103 (06) :2337-2342
[9]   Age-dependent changes in B lymphocyte development in man and mouse [J].
Ghia, P ;
Melchers, F ;
Rolink, AG .
EXPERIMENTAL GERONTOLOGY, 2000, 35 (02) :159-165
[10]   Age-dependent accumulation of monoclonal CD4+CD8+double positive T lymphocytes in the peripheral blood of the elderly [J].
Ghia, Paolo ;
Prato, Giuseppina ;
Stella, Stefania ;
Scielzo, Cristina ;
Geuna, Massimo ;
Caligaris-Cappio, Federico .
BRITISH JOURNAL OF HAEMATOLOGY, 2007, 139 (05) :780-790