Tailored approaches grounded on immunogenetic features for refined prognostication in chronic lymphocytic leukemia

被引：42

作者：

Baliakas, Panagiotis ^{[1
]}

Moysiadis, Theodoros ^{[2
]}

Hadzidimitriou, Anastasia ^{[1
,2
]}

Xochelli, Aliki ^{[1
,2
]}

Jeromin, Sabine ^{[3
]}

Agathangelidis, Andreas ^{[2
]}

Mattsson, Mattias ^{[1
]}

Sutton, Lesley-Ann ^{[1
]}

Minga, Eva ^{[2
]}

Scarfo, Lydia ^{[4
,5
]}

Rossi, Davide ^{[6
]}

Davis, Zadie ^{[7
]}

Villamor, Neus ^{[8
]}

Parker, Helen ^{[9
,10
]}

Kotaskova, Jana ^{[11
,12
]}

Stalika, Evangelia ^{[2
,13
,14
]}

Plevova, Karla ^{[11
,12
]}

Mansouri, Larry ^{[1
]}

Cortese, Diego ^{[1
]}

Navarro, Alba ^{[8
]}

Delgado, Julio ^{[15
]}

Larrayoz, Marta ^{[9
,10
]}

Young, Emma ^{[1
]}

Anagnostopoulos, Achilles ^{[13
,14
]}

Smedby, Karin E. ^{[16
]}

Juliusson, Gunnar ^{[17
]}

Sheehy, Oonagh ^{[18
]}

Catherwood, Mark ^{[18
]}

Strefford, Jonathan C. ^{[9
,10
]}

Stavroyianni, Niki ^{[13
,14
]}

Belessi, Chrysoula ^{[19
]}

Pospisilova, Sarka ^{[11
,12
]}

Oscier, David ^{[7
]}

Gaidano, Gianluca ^{[20
]}

Campo, Elias ^{[8
,21
]}

Haferlach, Claudia ^{[3
]}

Ghia, Paolo ^{[4
,5
]}

Rosenquist, Richard ^{[22
]}

Stamatopoulos, Kostas ^{[16
]}

机构：

[1] Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Uppsala, Sweden

[2] Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece

[3] MLL Munich Leukemia Lab, Munich, Germany

[4] IRCCS Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy

[5] Univ Vita Salute San Raffaele, Milan, Italy

[6] Oncol Inst Southern Switzerland, Bellinzona, Switzerland

[7] Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England

[8] Hosp Clin Barcelona, Hemopathol Unit, Barcelona, Spain

[9] Univ Southampton, Canc Res UK Ctr, Acad Unit Canc Sci, Canc Genon, Southampton, Hants, England

[10] Univ Southampton, Fac Med, Expt Canc Med Ctr, Southampton, Hants, England

[11] Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic

[12] Univ Hosp Brno, Brno, Czech Republic

[13] G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece

[14] G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece

[15] Hosp Clin Barcelona, Hematol Dept, Barcelona, Spain

[16] Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden

[17] Lund Univ & Hosp, Lund Stem Cell Ctr, Dept Hematol, Lund, Sweden

[18] Belfast City Hosp, Dept Hematooncol, Belfast, Antrim, North Ireland

[19] Nikea Gen Hosp, Hematol Dept, Piraeus, Greece

[20] Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy

[21] Univ Barcelona, Dept Pathol, Barcelona, Spain

[22] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

来源：

HAEMATOLOGICA | 2019年 / 104卷 / 02期

基金：

瑞典研究理事会;

关键词：

PREVIOUSLY UNTREATED PATIENTS; B-CELL RECEPTORS; STEREOTYPED IGHV3-21; GENOMIC ABERRATIONS; CLL; MUTATIONS; SURVIVAL; INDEX; GENE; CLASSIFICATION;

D O I：

10.3324/haematol.2018.195032

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Chronic lymphocytic leukemia (CLL) patients with differential somatic hypermutation status of the immunoglobulin heavy variable genes, namely mutated or unmutated, display fundamental clinico-biological differences. Considering this, we assessed prognosis separately within mutated (M-CLL) and unmutated (U-CLL) CLL in 3015 patients, hypothesizing that the relative significance of relevant indicators may differ between these two categories. Within Binet A M-CLL patients, besides TP53 abnormalities, trisomy 12 and stereotyped subset #2 membership were equivalently associated with the shortest time-to first -treatment and a treatment probability at Five and ten years after diagnosis of 40% and 55%, respectively; the remaining cases exhibited 5-year and 10-year treatment probability of 12% and 25%, respectively. Within Binet A U-CLL patients, besides TP53 abnormalities, del(11q) and/or ST3B1 mutations were associated with the shortest time-to-First treatment (5- and 10-year treatment probability: 78% and 98%, respectively); in the remaining cases, males had a significantly worse prognosis than females. In conclusion, the relative weight of indicators that can accurately risk stratify early-stage CLL patients differs depending on the somatic hypermutation status of the immunoglobulin heavy variable genes of each patient. This finding highlights the fact that compartmentalized approaches based on immunogenetic features are necessary to refine and tailor prognostication in CLL.

引用

页码：360 / 369

页数：10

共 52 条

[31] Novel agents in chronic lymphocytic leukemia [J].

Lamanna, Nicole ;

O'Brien, Sussan .

HEMATOLOGY-AMERICAN SOCIETY OF HEMATOLOGY EDUCATION PROGRAM, 2016, :137-145

[32] Mutations driving CLL and their evolution in progression and relapse [J].

Landau, Dan A. ;

Tausch, Eugen ;

Taylor-Weiner, Amaro N. ;

Stewart, Chip ;

Reiter, Johannes G. ;

Bahlo, Jasmin ;

Kluth, Sandra ;

Bozic, Ivana ;

Lawrence, Mike ;

Boettcher, Sebastian ;

Carter, Scott L. ;

Cibulskis, Kristian ;

Mertens, Daniel ;

Sougnez, Carrie L. ;

Rosenberg, Mara ;

Hess, Julian M. ;

Edelmann, Jennifer ;

Kless, Sabrina ;

Kneba, Michael ;

Ritgen, Matthias ;

Fink, Anna ;

Fischer, Kirsten ;

Gabriel, Stacey ;

Lander, Eric S. ;

Nowak, Martin A. ;

Doehner, Hartmut ;

Hallek, Michael ;

Neuberg, Donna ;

Getz, Gad ;

Stilgenbauer, Stephan ;

Wu, Catherine J. .

NATURE, 2015, 526 (7574) :525-U132

[33] Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia [J].

Landau, Dan A. ;

Carter, Scott L. ;

Stojanov, Petar ;

McKenna, Aaron ;

Stevenson, Kristen ;

Lawrence, Michael S. ;

Sougnez, Carrie ;

Stewart, Chip ;

Sivachenko, Andrey ;

Wang, Lili ;

Wan, Youzhong ;

Zhang, Wandi ;

Shukla, Sachet A. ;

Vartanov, Alexander ;

Fernandes, Stacey M. ;

Saksena, Gordon ;

Cibulskis, Kristian ;

Tesar, Bethany ;

Gabriel, Stacey ;

Hacohen, Nir ;

Meyerson, Matthew ;

Lander, Eric S. ;

Neuberg, Donna ;

Brown, Jennifer R. ;

Getz, Gad ;

Wu, Catherine J. .

CELL, 2013, 152 (04) :714-726

[34] Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations [J].

Ljungstrom, Viktor ;

Cortese, Diego ;

Young, Emma ;

Pandzic, Tatjana ;

Mansouri, Larry ;

Plevova, Karla ;

Ntoufa, Stavroula ;

Baliakas, Panagiotis ;

Clifford, Ruth ;

Sutton, Lesley-Ann ;

Blakemore, Stuart J. ;

Stavroyianni, Niki ;

Agathangelidis, Andreas ;

Rossi, Davide ;

Hoglund, Martin ;

Kotaskova, Jana ;

Juliusson, Gunnar ;

Belessi, Chrysoula ;

Chiorazzi, Nicholas ;

Panagiotidis, Panagiotis ;

Langerak, Anton W. ;

Smedby, Karin E. ;

Oscier, David ;

Gaidano, Gianluca ;

Schuh, Anna ;

Davi, Frederic ;

Pott, Christiane ;

Strefford, Jonathan C. ;

Trentin, Livio ;

Pospisilova, Sarka ;

Ghia, Paolo ;

Stamatopoulos, Kostas ;

Sjoblom, Tobias ;

Rosenquist, Richard .

BLOOD, 2016, 127 (08) :1007-1016

[35] High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors [J].

Marincevic, Millaray ;

Cahill, Nicola ;

Gunnarsson, Rebeqa ;

Isaksson, Anders ;

Mansouri, Mahmoud ;

Goransson, Hanna ;

Rasmussen, Markus ;

Jansson, Mattias ;

Ryan, Fergus ;

Karlsson, Karin ;

Adami, Hans-Olov ;

Davi, Fred ;

Jurlander, Jesper ;

Juliusson, Gunnar ;

Stamatopoulos, Kostas ;

Rosenquist, Richard .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2010, 95 (09) :1519-1525

[36] Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemia [J].

Morabito, Fortunato ;

Cutrona, Giovanna ;

Gentile, Massimo ;

Matis, Serena ;

Todoerti, Katia ;

Colombo, Monica ;

Sonaglio, Claudia ;

Fabris, Sonia ;

Reverberi, Daniele ;

Megna, Mauro ;

Spriano, Mauro ;

Lucia, Eugenio ;

Rossi, Edoardo ;

Callea, Vincenzo ;

Mazzone, Carla ;

Festini, Gianluca ;

Zupo, Simonetta ;

Molica, Stefano ;

Neri, Antonino ;

Ferrarini, Manlio .

BRITISH JOURNAL OF HAEMATOLOGY, 2009, 146 (01) :44-53

[37] Distinct Innate Immunity Pathways to Activation and Tolerance in Subgroups of Chronic Lymphocytic Leukemia with Distinct Immunoglobulin Receptors [J].

Ntoufa, Stavroula ;

Vardi, Anna ;

Papakonstantinou, Nikos ;

Anagnostopoulos, Achilles ;

Aleporou-Marinou, Vassiliki ;

Belessi, Chrysoula ;

Ghia, Paolo ;

Caligaris-Cappio, Federico ;

Muzio, Marta ;

Stamatopoulos, Kostas .

MOLECULAR MEDICINE, 2012, 18 (09) :1281-1291

[38] Multivariate analysis of prognostic factors in CLL:: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors [J].

Oscier, DG ;

Gardiner, AC ;

Mould, SJ ;

Glide, S ;

Davis, ZA ;

Ibbotson, RE ;

Corcoran, MM ;

Chapman, RM ;

Thomas, PW ;

Copplestone, JA ;

Orchard, JA ;

Hamblin, TJ .

BLOOD, 2002, 100 (04) :1177-1184

[39] CLINICAL STAGING OF CHRONIC LYMPHOCYTIC LEUKEMIA [J].

RAI, KR ;

SAWITSKY, A ;

CRONKITE, EP ;

CHANANA, AD ;

LEVY, RN ;

PASTERNACK, BS .

BLOOD, 1975, 46 (02) :219-234

[40] Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia [J].

Roberts, Andrew W. ;

Davids, Matthew S. ;

Pagel, John M. ;

Kahl, Brad S. ;

Puvvada, Soham D. ;

Gerecitano, John F. ;

Kipps, Thomas J. ;

Anderson, Mary Ann ;

Brown, Jennifer R. ;

Gressick, Lori ;

Wong, Shekman ;

Dunbar, Martin ;

Zhu, Ming ;

Desai, Monali B. ;

Cerri, Elisa ;

Enschede, Sari Heitner ;

Humerickhouse, Rod A. ;

Wierda, William G. ;

Seymour, John F. .

NEW ENGLAND JOURNAL OF MEDICINE, 2016, 374 (04) :311-322

← 1 2 3 4 5 6 →