Molecular analysis of light-chain switch and acute lymphoblastic leukemia transformation in two follicular lymphomas: implications for lymphomagenesis.
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.
Kobrin
Carol
C
Intramural Research Support Program, SAIC-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, USA.
Cha
Soung-Chul
SC
Qin
Hong
H
Raffeld
Mark
M
Fend
Falko
F
Quintanilla-Martinez
Leticia
L
Grove
Sheldon
S
Jaffe
Elaine S
ES
Kwak
Larry W
LW
D000328:Adult; D001706:Biopsy; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002999:Clone Cells / Q000473:pathology; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D017578:Immunoglobulin Class Switching; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D016393:Lymphoma, B-Cell / Q000209:etiology*; D008224:Lymphoma, Follicular / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000209:etiology / Q000473:pathology*
D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains