Am J Blood Res 2011;1(1):13-21
Original Article
Specific chromosomal IG translocations have different prognoses in chronic
lymphocytic leukemia
Florence Nguyen-Khac, Elise Chapiro, Claude Lesty, Aurore Grelier, Isabelle Luquet, Isabelle Radford-Weiss, Christine
Lefebvre, Sandra Fert-Ferrer, Evelyne Callet-Bauchu, Eric Lippert, Victoria Raggueneau, Lucienne Michaux, Carole Barin,
Marie-Agnes Collonge-Rame, Francine Mugneret, Virginie Eclache, Sylvie Taviaux, Nicole Dastugue, Steven Richebourg,
Stéphanie Struski, Pascaline Talmant, Laurence Baranger, Nathalie Gachard, Carine Gervais, Benoit Quilichini, Catherine
Settegrana, Karim Maloum, Frederic Davi, Hélène Merle-Béral, on the behalf of the Groupe Francophone de Cytogénétique
Hématologique
Service d’Hématologie Biologique, Hôpital Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, France; INSERM
U872 ; Université Pierre et Marie Curie-Paris 6, France; Laboratoire de Cytogénétique, Hôpital de Reims, France; Laboratoire
de Cytogénétique, Hôpital Necker-Enfants Malades, France; Laboratoire de Cytogénétique, Hôpital de Grenoble, France;
Laboratoire de Cytogénétique, Hôpital de Chambéry, France; Laboratoire de Cytogénétique, Hôpital Lyon-Sud, France;
Laboratoire d’Hématologie, CHU Bordeaux, and Laboratoire hématopoïèse leucémique et Cibles Thérapeutiques,
INSERMU876, Université Bordeaux2, France; Laboratoire de Cytogénétique, Hôpital A Mignot, Versailles, France; Center for
Human Genetics, KULeuven, Belgium; Laboratoire de Cytogénétique, Hôpital de Tours, France; Laboratoire de
Cytogénétique, CHU Besançon, France; Laboratoire de Cytogénétique, Dijon, France; Hématologie Biologique, Hôpital
Avicenne, Université Paris 13, Bobigny, France; Laboratoire de Cytogénétique, Montpellier, France; Génétique des
Hémopathies, CHU Toulouse, France; Laboratoire de Cytogénétique, Hôpital de Nantes, France; Laboratoire de
Cytogénétique, CHU Angers, France; Laboratoire de Cytogénétique, Limoges, France; Laboratoire de Cytogénétique, CHU
Strasbourg, France; Laboratoire Biomnis, Lyon, France.
Received March 16, 2011; accepted April 10, 2011; Epub April 15, 2011; published June 15, 2011
Abstract: Background: Chromosomal translocations are usually analyzed as a single entity, and are associated with a poor
outcome in chronic lymphocytic leukemia. Translocations involving immunoglobulin genes are recurrent, but uncommon
(<5%), and their individual prognosis is not clear. The two most frequent partners are BCL2 (18q21) and BCL3 (19q13).
Designs and methods: Herein, 75 cases are reported of chronic lymphocytic leukemia and t(14;18) (BCL2-CLLs). Our series
benefits from morphological, immunological and cytogenetical reviews. The IGHV status analyses were performed by
referring laboratories. Comparison was made with our previously published series of chronic lymphocytic leukemia patients
with t(14;19) (BCL3-CLLs, n=29). Results: Compared with BCL3-CLLs, lymphocytosis was lower in BCL2-CLLs (p<0.008),
and splenomegaly was less frequent (p<0.0001). There were more “typical” morphologies (p<0.005) and Matutes scores >4
(p<0.001) in the BCL2-CLLs group, and less CD38 expression (p<0.04). More variant BCL2-translocations were observed (t
(18;22), n=11; 2t(2;18), n=2; p<0.02), and BCL2-translocation was frequently single (p<0.002). Complex karyotypes (p<0.02),
trisomy 12 (p<0.03), 6q deletion (p<0.002) and TP53 deletion (p<0.02) were less frequent in BCL2-CLLs, whereas 13q
deletion was more frequent (p<0.005). The IGHV gene was frequently mutated in BCL2-CLLs (p<0.0001). Treatment-free
survival was longer in BCL2-CLLs (p<0.0001). Conclusions: BCL2-CLLs express CD5 and lack expression of CD38, and
have a Matutes score >4, frequent trisomy 12, no ATM and 6q deletions, and a mutated IGHV status. Compared to BCL3-
CLLs, BCL2-CLLs are much less aggressive, indicating that identifying individual translocations and cytogenetic partners
would allow improved patient stratification. (AJBR1103002).
Keywords: Chronic lymphocytic leukemia, IGH, BCL2, chromosomal translocation
Full Text PDF
Address all correspondence to:
Florence Nguyen-Khac, MD-PhD
Service Hématologie Biologique
Groupe Hospitalier Pitié-Salpêtrière
47-83, Bvd de l’Hôpital
75013 Paris, France.
Phone: 33(1)42162451, Fax: 33(1)42162453
E-mail: Florence.nguyen-khac@psl.aphp.fr
Original Article
Specific chromosomal IG translocations have different prognoses in chronic
lymphocytic leukemia
Florence Nguyen-Khac, Elise Chapiro, Claude Lesty, Aurore Grelier, Isabelle Luquet, Isabelle Radford-Weiss, Christine
Lefebvre, Sandra Fert-Ferrer, Evelyne Callet-Bauchu, Eric Lippert, Victoria Raggueneau, Lucienne Michaux, Carole Barin,
Marie-Agnes Collonge-Rame, Francine Mugneret, Virginie Eclache, Sylvie Taviaux, Nicole Dastugue, Steven Richebourg,
Stéphanie Struski, Pascaline Talmant, Laurence Baranger, Nathalie Gachard, Carine Gervais, Benoit Quilichini, Catherine
Settegrana, Karim Maloum, Frederic Davi, Hélène Merle-Béral, on the behalf of the Groupe Francophone de Cytogénétique
Hématologique
Service d’Hématologie Biologique, Hôpital Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, France; INSERM
U872 ; Université Pierre et Marie Curie-Paris 6, France; Laboratoire de Cytogénétique, Hôpital de Reims, France; Laboratoire
de Cytogénétique, Hôpital Necker-Enfants Malades, France; Laboratoire de Cytogénétique, Hôpital de Grenoble, France;
Laboratoire de Cytogénétique, Hôpital de Chambéry, France; Laboratoire de Cytogénétique, Hôpital Lyon-Sud, France;
Laboratoire d’Hématologie, CHU Bordeaux, and Laboratoire hématopoïèse leucémique et Cibles Thérapeutiques,
INSERMU876, Université Bordeaux2, France; Laboratoire de Cytogénétique, Hôpital A Mignot, Versailles, France; Center for
Human Genetics, KULeuven, Belgium; Laboratoire de Cytogénétique, Hôpital de Tours, France; Laboratoire de
Cytogénétique, CHU Besançon, France; Laboratoire de Cytogénétique, Dijon, France; Hématologie Biologique, Hôpital
Avicenne, Université Paris 13, Bobigny, France; Laboratoire de Cytogénétique, Montpellier, France; Génétique des
Hémopathies, CHU Toulouse, France; Laboratoire de Cytogénétique, Hôpital de Nantes, France; Laboratoire de
Cytogénétique, CHU Angers, France; Laboratoire de Cytogénétique, Limoges, France; Laboratoire de Cytogénétique, CHU
Strasbourg, France; Laboratoire Biomnis, Lyon, France.
Received March 16, 2011; accepted April 10, 2011; Epub April 15, 2011; published June 15, 2011
Abstract: Background: Chromosomal translocations are usually analyzed as a single entity, and are associated with a poor
outcome in chronic lymphocytic leukemia. Translocations involving immunoglobulin genes are recurrent, but uncommon
(<5%), and their individual prognosis is not clear. The two most frequent partners are BCL2 (18q21) and BCL3 (19q13).
Designs and methods: Herein, 75 cases are reported of chronic lymphocytic leukemia and t(14;18) (BCL2-CLLs). Our series
benefits from morphological, immunological and cytogenetical reviews. The IGHV status analyses were performed by
referring laboratories. Comparison was made with our previously published series of chronic lymphocytic leukemia patients
with t(14;19) (BCL3-CLLs, n=29). Results: Compared with BCL3-CLLs, lymphocytosis was lower in BCL2-CLLs (p<0.008),
and splenomegaly was less frequent (p<0.0001). There were more “typical” morphologies (p<0.005) and Matutes scores >4
(p<0.001) in the BCL2-CLLs group, and less CD38 expression (p<0.04). More variant BCL2-translocations were observed (t
(18;22), n=11; 2t(2;18), n=2; p<0.02), and BCL2-translocation was frequently single (p<0.002). Complex karyotypes (p<0.02),
trisomy 12 (p<0.03), 6q deletion (p<0.002) and TP53 deletion (p<0.02) were less frequent in BCL2-CLLs, whereas 13q
deletion was more frequent (p<0.005). The IGHV gene was frequently mutated in BCL2-CLLs (p<0.0001). Treatment-free
survival was longer in BCL2-CLLs (p<0.0001). Conclusions: BCL2-CLLs express CD5 and lack expression of CD38, and
have a Matutes score >4, frequent trisomy 12, no ATM and 6q deletions, and a mutated IGHV status. Compared to BCL3-
CLLs, BCL2-CLLs are much less aggressive, indicating that identifying individual translocations and cytogenetic partners
would allow improved patient stratification. (AJBR1103002).
Keywords: Chronic lymphocytic leukemia, IGH, BCL2, chromosomal translocation
Full Text PDF
Address all correspondence to:
Florence Nguyen-Khac, MD-PhD
Service Hématologie Biologique
Groupe Hospitalier Pitié-Salpêtrière
47-83, Bvd de l’Hôpital
75013 Paris, France.
Phone: 33(1)42162451, Fax: 33(1)42162453
E-mail: Florence.nguyen-khac@psl.aphp.fr
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