Richter's May Develop in Both Mutated and Unmutated CLL, But Pathogenesis Differ

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Leukemia. 2003 Dec 11 [Epub ahead of print].

Relationship between the mutational status of V(H) genes and

pathogenesis of diffuse large B-cell lymphoma in Richter's syndrome.

Timar B, Fulop Z, Csernus B, Angster C, Bognar A, Szepesi A, Kopper

L, Matolcsy A.

11st Department of Pathology and Experimental Cancer Research,

Faculty of Medicine, Semmelweis University, Budapest, Hungary.

Patients with chronic lymphocytic leukemia (CLL) may develop diffuse

large B-cell lymphoma (DLBL), also known as Richter's syndrome.

Mutational status of immunoglobulin (Ig) heavy-chain variable region

(V(H)) genes have prognostic impact in CLL. Patients with mutated V

(H) genes have a stable disease, whereas patients with unmutated V(H)

gene have more aggressive disease. The mutational status of CLLs that

transform to DLBL is unknown.

To reveal whether Richter's syndrome occurs in CLLs with mutated or

unmutated V(H) genes, we have performed mutational analysis on serial

specimens from eight patients. CLL and DLBL tumorclones were

identical in five cases and they were different in three cases. Six

CLLs expressed unmutated and two cases expressed mutated V(H) genes.

In five of the six unmutated CLLs, the DLBL clones evolved from CLL

tumorclones and the V(H) genes expressed by DLBLs were also

unmutated. In one unmutated and two mutated CLLs, the DLBLs expressed

mutated V(H) genes, but in these three cases the DLBL tumorclones

developed as independent secondary neoplasm. These results suggest

that Richter's syndrome may develop in both mutated or unmutated

CLLs, but clonal transformation of CLL to DLBL occur only in the

unmutated subgroup of CLL.

Leukemia advance online publication, 11 December 2003;

doi:10.1038/sj.leu.2403249

PMID: 14671632 [PubMed - as supplied by publisher]