TY - JOUR
T1 - Molecular analysis of light-chain switch and acute lymphoblastic leukemia transformation in two follicular lymphomas
T2 - Implications for lymphomagenesis
AU - Kobrin, Carol
AU - Cha, Soung Chul
AU - Qin, Hong
AU - Raffeld, Mark
AU - Fend, Falko
AU - Quintanilla-Martinez, Leticia
AU - Grove, Sheldon
AU - Jaffe, Elaine S.
AU - Kwak, Larry W.
N1 - Funding Information:
Correspondence: Larry W. Kwak, Department of Lymphoma and Myeloma, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 429, Houston, Texas 77030, USA. Tel: 713 745 4244. Fax: 713 563 4625. E-mail: lkwak@mdanderson.org This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. N01-CO-56000. The publisher or recipient acknowledges right of the U.S. Government to retain a nonexclusive, royalty-free license in and to any copyright covering the article. The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
PY - 2006/8
Y1 - 2006/8
N2 - We observed novel transformations of follicular lymphoma (FL), first, a switch in immunoglobulin (Ig) light chain, and second, transformation of FL to acute lymphoblastic leukemia (ALL). Each set of tumors shared a common clonal origin, as demonstrated by expression of identical, unique CDR IIIH sequences, shared somatic mutations in JH, and identical bcl-2 translocation breakpoints of microdissected ALL cells. Molecular analysis of lambda V-gene expression demonstrated lambda-bearing cells in the original kappa tumor, while expansion of the lambda subclone at relapse occurred after active immunotherapy targeting the Ig receptor. These exceptional cases are compatible with a more contemporary model of lymphomagenesis in which critical events originate from genetic mechanisms which normally occur in germinal center (GC) B cells and challenge the current paradigm of parallel generation of subclones from an early, pre-GC precursor. It is also possible that the outgrowth of these variants was a consequence of immunoselection.
AB - We observed novel transformations of follicular lymphoma (FL), first, a switch in immunoglobulin (Ig) light chain, and second, transformation of FL to acute lymphoblastic leukemia (ALL). Each set of tumors shared a common clonal origin, as demonstrated by expression of identical, unique CDR IIIH sequences, shared somatic mutations in JH, and identical bcl-2 translocation breakpoints of microdissected ALL cells. Molecular analysis of lambda V-gene expression demonstrated lambda-bearing cells in the original kappa tumor, while expansion of the lambda subclone at relapse occurred after active immunotherapy targeting the Ig receptor. These exceptional cases are compatible with a more contemporary model of lymphomagenesis in which critical events originate from genetic mechanisms which normally occur in germinal center (GC) B cells and challenge the current paradigm of parallel generation of subclones from an early, pre-GC precursor. It is also possible that the outgrowth of these variants was a consequence of immunoselection.
KW - Idiotype vaccine
KW - Immune selection
KW - Immunoglobulin (Ig) receptor revision
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U2 - 10.1080/10428190600612909
DO - 10.1080/10428190600612909
M3 - Article
C2 - 16966263
AN - SCOPUS:33748567437
SN - 1042-8194
VL - 47
SP - 1523
EP - 1534
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 8
ER -