Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome

被引：208

作者：

Chigrinova, Ekaterina ^{[1
,2
]}

Rinaldi, Andrea ^{[1
]}

Kwee, Ivo ^{[1
,3
,4
]}

Rossi, Davide ^{[5
]}

Rancoita, Paola M. V. ^{[1
,3
]}

Strefford, Jonathan C. ^{[6
]}

Oscier, David ^{[7
]}

Stamatopoulos, Kostas ^{[8
,9
,10
]}

Papadaki, Theodora ^{[8
,9
]}

Berger, Francoise ^{[11
]}

Young, Ken H. ^{[12
]}

Murray, Fiona ^{[13
]}

Rosenquist, Richard ^{[13
]}

Greiner, Timothy C. ^{[13
]}

Chan, Wing C. ^{[14
]}

Orlandi, Ester M. ^{[15
,16
]}

Lucioni, Marco ^{[15
,16
]}

Marasca, Roberto ^{[17
]}

Inghirami, Giorgio ^{[18
]}

Ladetto, Marco ^{[19
]}

Forconi, Francesco ^{[6
,20
]}

Cogliatti, Sergio ^{[21
]}

Votavova, Hana ^{[22
]}

Swerdlow, Steven H. ^{[23
]}

Stilgenbauer, Stephan ^{[24
]}

Piris, Miguel A. ^{[25
]}

Matolcsy, Andras ^{[26
]}

Spagnolo, Dominic ^{[27
]}

Nikitin, Eugene ^{[28
]}

Zamo, Alberto ^{[29
]}

Gattei, Valter ^{[30
]}

Bhagat, Govind ^{[31
,32
]}

Ott, German ^{[33
,34
]}

Zucca, Emanuele ^{[2
]}

Gaidano, Gianluca ^{[5
]}

Bertoni, Francesco ^{[1
,2
]}

机构：

[1] IOR Inst Oncol Res, Lymphoma & Genom Res Program, Bellinzona, Switzerland

[2] Oncol Inst Southern Switzerland IOSI, Bellinzona, Switzerland

[3] Dalle Molle Inst Artificial Intelligence IDSIA, Manno, Switzerland

[4] Swiss Inst Bioinformat, Lausanne, Switzerland

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

[6] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England

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

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

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

[10] CERTH, Inst Appl Biosci, Thessaloniki, Greece

[11] Univ Lyon 1, Ctr Hosp Lyon Sud, Hosp Civils Lyon, F-69365 Lyon, France

[12] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA

[13] Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, Uppsala, Sweden

[14] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA

[15] Univ Pavia, Policlin San Matteo, Fdn Ist Ricovero & Cura Carattere Sci, Dept Hematol Oncol,Hematol Unit, I-27100 Pavia, Italy

[16] Univ Pavia, Policlin San Matteo, Div Pathol, Fdn Ist Ricovero & Cura Carattere Sci, I-27100 Pavia, Italy

[17] Univ Modena & Reggio Emilia, Div Hematol, Modena, Italy

[18] Univ Turin, Dept Pathol, Ctr Expt Res & Med Studies CeRMS, Turin, Italy

[19] Univ Turin, Div Hematol, AOU San Giovanni Battista, Turin, Italy

[20] Univ Siena, Div Haematol, I-53100 Siena, Italy

[21] St Gallen Hosp, St Gallen, Switzerland

[22] Inst Hematol & Blood Transfus, Dept Mol Genet, CR-12820 Prague, Czech Republic

[23] Univ Pittsburgh, Sch Med, Dept Pathol, Div Hematopathol, Pittsburgh, PA USA

[24] Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany

[25] Hosp Univ Marques Valdecilla, Santander, Spain

[26] Semmelweis Univ, Fac Med, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary

[27] PathWest Lab Med WA, Dept Pathol, Nedlands, WA, Australia

[28] Hematol Res Ctr Russia, Moscow, Russia

[29] Univ Verona, Dept Pathol, I-37100 Verona, Italy

[30] Ctr Riferimento Oncol, Clin & Expt Oncohematol Unit, I-33081 Aviano, Italy

[31] Columbia Univ, Med Ctr, New York, NY USA

[32] New York Presbyterian Hosp, New York, NY USA

[33] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany

[34] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany

来源：

BLOOD | 2013年 / 122卷 / 15期

关键词：

B-CELL LYMPHOMAS; NOTCH1; MUTATIONS; CODING GENOME; PROGNOSIS; INACTIVATION; PATHOGENESIS; DELETIONS; INSIGHTS; REVEALS; CLL;

D O I：

10.1182/blood-2013-03-489518

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). Although RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the preexisting CLL, the mechanisms leading to RS have not been clarified. To better understand the pathogenesis of RS, we analyzed a series of cases including 59 RS, 28 CLL phase of RS, 315 CLL, and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell-cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL phase, being present in approximately one half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. Although RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL phase preceding RS had not a generalized increase in genomic complexity compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.

引用

页码：2673 / 2682

页数：10

共 47 条

[1] NOTCH1 mutations in CLL associated with trisomy 12 [J].

Balatti, Veronica ;

Bottoni, Arianna ;

Palamarchuk, Alexey ;

Alder, Hansjuerg ;

Rassenti, Laura Z. ;

Kipps, Thomas J. ;

Pekarsky, Yuri ;

Croce, Carlo M. .

BLOOD, 2012, 119 (02) :329-331

[2] Genetic imbalances in progressed B-cell chronic lymphocytic leukemia and transformed large-cell lymphoma (Richter's syndrome) [J].

Beà, S ;

López-Guillermo, A ;

Ribas, M ;

Puig, X ;

Pinyol, M ;

Carrió, A ;

Zamora, L ;

Sole, F ;

Bosch, F ;

Stilgenbauer, S ;

Colomer, D ;

Miró, R ;

Montserrat, E ;

Campo, E .

AMERICAN JOURNAL OF PATHOLOGY, 2002, 161 (03) :957-968

[3] Genome wide DNA-profiling of HIV-related B-cell lymphomas [J].

Capello, Daniela ;

Scandurra, Marta ;

Poretti, Giulia ;

Rancoita, Paola M. V. ;

Mian, Michael ;

Gloghini, Annunziata ;

Deambrogi, Clara ;

Martini, Maurizio ;

Rossi, Davide ;

Greiner, Timothy C. ;

Chan, Wing C. ;

Ponzoni, Maurilio ;

Moreno, Santiago M. ;

Piris, Miguel A. ;

Canzonieri, Vincenzo ;

Spina, Michele ;

Tirelli, Umberto ;

Inghirami, Giorgio ;

Rinaldi, Andrea ;

Zucca, Emanuele ;

Favera, Riccardo D. ;

Cavalli, Franco ;

Larocca, Luigi Maria ;

Kwee, Ivo ;

Carbone, Antonino ;

Gaidano, Gianluca ;

Bertoni, Francesco .

BRITISH JOURNAL OF HAEMATOLOGY, 2010, 148 (02) :245-255

[4] Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia [J].

Cobo, F ;

Martínez, A ;

Pinyol, M ;

Hernández, L ;

Gómez, M ;

Beá, S ;

Esteve, J ;

Rozman, M ;

Bosch, F ;

López-Guillermo, A ;

Montserrat, E ;

Campo, E .

LEUKEMIA, 2002, 16 (06) :1028-1034

[5] MYC on the Path to Cancer [J].

Dang, Chi V. .

CELL, 2012, 149 (01) :22-35

[6] MGA, a suppressor of MYC, is recurrently inactivated in high risk chronic lymphocytic leukemia [J].

De Paoli, Lorenzo ;

Cerri, Michaela ;

Monti, Sara ;

Rasi, Silvia ;

Spina, Valeria ;

Bruscaggin, Alessio ;

Greco, Mariangela ;

Ciardullo, Carmela ;

Fama, Rosella ;

Cresta, Stefania ;

Maffei, Rossana ;

Ladetto, Marco ;

Martini, Maurizio ;

Laurenti, Luca ;

Forconi, Francesco ;

Marasca, Roberto ;

Larocca, Luigi M. ;

Bertoni, Francesco ;

Gaidano, Gianluca ;

Rossi, Davide .

LEUKEMIA & LYMPHOMA, 2013, 54 (05) :1087-1090

[7] Molecular distinctions between pediatric and adult mature B-cell non-Hodgkin lymphomas identified through genomic profiling [J].

Deffenbacher, Karen E. ;

Iqbal, Javeed ;

Sanger, Warren ;

Shen, Yulei ;

Lachel, Cynthia ;

Liu, Zhongfeng ;

Liu, Yanyan ;

Lim, Megan S. ;

Perkins, Sherrie L. ;

Fu, Kai ;

Smith, Lynette ;

Lynch, James ;

Staudt, Louis M. ;

Rimsza, Lisa M. ;

Jaffe, Elaine ;

Rosenwald, Andreas ;

Ott, German K. ;

Delabie, Jan ;

Campo, Elias ;

Gascoyne, Randy D. ;

Cairo, Mitchell S. ;

Weisenburger, Dennis D. ;

Greiner, Timothy C. ;

Gross, Thomas G. ;

Chan, Wing C. .

BLOOD, 2012, 119 (16) :3757-3766

[8] NOTCH1 mutations in+12 chronic lymphocytic leukemia (CLL) confer an unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of+12 CLL [J].

Del Giudice, Ilaria ;

Rossi, Davide ;

Chiaretti, Sabina ;

Marinelli, Marilisa ;

Tavolaro, Simona ;

Gabrielli, Sara ;

Laurenti, Luca ;

Marasca, Roberto ;

Rasi, Silvia ;

Fangazio, Marco ;

Guarini, Anna ;

Gaidano, Gianluca ;

Foa, Robin .

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2012, 97 (03) :437-441

[9] High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations [J].

Edelmann, Jennifer ;

Holzmann, Karlheinz ;

Miller, Florian ;

Winkler, Dirk ;

Buehler, Andreas ;

Zenz, Thorsten ;

Bullinger, Lars ;

Kuehn, Michael W. M. ;

Gerhardinger, Andreas ;

Bloehdorn, Johannes ;

Radtke, Ina ;

Su, Xiaoping ;

Ma, Jing ;

Pounds, Stanley ;

Hallek, Michael ;

Lichter, Peter ;

Korbel, Jan ;

Busch, Raymonde ;

Mertens, Daniel ;

Downing, James R. ;

Stilgenbauer, Stephan ;

Doehner, Hartmut .

BLOOD, 2012, 120 (24) :4783-4794

[10] Analysis of the chronic lymphocytic leukemia coding genome: role of NOTCH1 mutational activation [J].

Fabbri, Giulia ;

Rasi, Silvia ;

Rossi, Davide ;

Trifonov, Vladimir ;

Khiabanian, Hossein ;

Ma, Jing ;

Grunn, Adina ;

Fangazio, Marco ;

Capello, Daniela ;

Monti, Sara ;

Cresta, Stefania ;

Gargiulo, Ernesto ;

Forconi, Francesco ;

Guarini, Anna ;

Arcaini, Luca ;

Paulli, Marco ;

Laurenti, Luca ;

Larocca, Luigi M. ;

Marasca, Roberto ;

Gattei, Valter ;

Oscier, David ;

Bertoni, Francesco ;

Mullighan, Charles G. ;

Foa, Robin ;

Pasqualucci, Laura ;

Rabadan, Raul ;

Dalla-Favera, Riccardo ;

Gaidano, Gianluca .

JOURNAL OF EXPERIMENTAL MEDICINE, 2011, 208 (07) :1389-1401

← 1 2 3 4 5 →