[Clonality analysis and mutational status of IgVH gene in Hodgkin variant of Richter syndrome].
OBJECTIVE
To detect the clonal relationship, the rearrangement, and the mutational status of IgVH gene; the influence of these molecular characteristics on the clinical outcome in Hodgkin variant of Richter syndrome; and the possible molecular pathogenesis in this transformation.


METHODS
The clonal rearrangements and mutational status of IgVH genes were analyzed in Hodgkin variant of Richter syndrome and B-CLL with Reed-Stemberg (R-S)-like cells by GeneScan analysis and sequencing. Semi-nest PCR based on laser capture microdissection was utilized to compare the clonal relationship between B-CLL and R-S/R-Slike cells. Immunohistochemical staining was used to detect the different expressions of ZAP70, p53, IRF-4 and LMP1 in the two components.


RESULTS
(1) 5/6 B-CLL cases transformed to Hodgkin lymphoma (HL)/R-S-like cells carried the mutated IgVH genes; (2) 2 cases of R-S cells and 1 case of R-S-like cells were clonally distinct from B-CLL clone and express LMP1, whereas 1 case of R-S-like cells was relating to the surrounding B-CLL cells and did not express LMP1; (3) 2/6 B-CLL cases transformed to HL convey VH4-34 and VH3-48 respectively.


CONCLUSIONS
(1) Richter transformation to HL/R-S-like cells evolves from the B-CLL which originates from the germinal center or post germinal center B cells, indicating that different lymphoma cells of different subtypes in Richter syndrome come from different B cell lineage and possibly involve a different pathogenesis and pathway; (2) HL and R-S-like cells evolve from either the B-CLL clone or may develop as a clonally unrelated lymphoma, the independent secondary malignancies are appear to be EBV-positive, possibly as a consequence of the underlying immunodeficiency; (3) The biased usage of IgVH genes suggested a role of antigens involved in the HL variant of Richter syndrome.
Mao
Zheng-rong
ZR
Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310058, China. maozr@zju.edu.cn
Rosenwald
Andreas
A
Zhang
Suo-jiang
SJ
Zhou
Ren
R
Mueller-Hermelink
Hans Konrad
HK
D000368:Aged; D000369:Aged, 80 and over; D002999:Clone Cells / Q000473:pathology; D005260:Female; D004854:Herpesvirus 4, Human; D006689:Hodgkin Disease / Q000145:classification / Q000235:genetics* / Q000473:pathology / Q000821:virology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016539:Reed-Sternberg Cells / Q000473:pathology*; D013577:Syndrome
D007135:Immunoglobulin Variable Region