Del(20q) in Patients with Chronic Lymphocytic Leukemia Is Associated with Prior Chemotherapy, Atypical Morphology, ZAP70 Expression, and Unmutated IGHV Genes.
C Cameron Yin, Gary Lu, L Jeffrey Medeiros, Xiaoli Feng, Michael J Keating, Lynne V Abruzzo. UT MD Anderson Cancer Center, Houston, TX
Background: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm with distinctive morphologic, immunophenotypic and molecular genetic features. Common cytogenetic abnormalities include deletions of chromosomes 11q22.3, 13q14.3 and 17p13.1, and trisomy 12. Interstitial deletion of the long arm of chromosome 20, del(20)(q11.2q13.1), a common recurrent cytogenetic abnormality in myeloid neoplasms, has rarely been described in lymphoid neoplasms. We report clinicopathologic, immunophenotypic and molecular genetic features of 41 CLL/SLL cases associated with del(20q), the largest series to date.
Design: We reviewed clinical data, bone marrow (BM) morphology, and immunostains. We performed flow cytometry immunophenotyping, conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis, and immunoglobulin heavy chain variable region (IGHV) gene sequence analysis.
Results: We identified 41 CLL/SLL cases with del(20q) representing 1% of all CLL/SLL (35 men, 6 women, median age of 55 years at diagnosis, range 32-77). 31 patients (76%) had previous chemotherapy. Upon presentation to our hospital, 13 were Rai stage I, 5 stage II, 5 stage III and 18 stage IV. Lymphocyte morphology was atypical in 18 (44%) with plasmacytoid differentiation and/or irregular nuclei; 9 had increased prolymphocytes (³5%). 39/41 showed typical immunophenotypes. Of 20 cases tested, 19 expressed ZAP70 and 19 showed unmutated IGHV genes. Conventional karyotyping identified del(20q) as the sole abnormality in 31, and as part of a complex karyotype in 10. In 16 cases, karyotypes before therapy were negative for del(20q). FISH analysis in 26 cases revealed del(13q) in 12, del(11q) in 9, +12 in 8 and del(17p) in 1. All patients received chemotherapy; 8 had BM transplantation. At the time of del(20q), 4 had clinical and morphologic evidence of myelodysplastic syndrome (MDS). Of these, 1 died of acute myeloid leukemia, 2 died of CLL/SLL, and 1 is alive with MDS/CLL. With a median follow-up of 94 months (range, 18-228), none of the rest have developed a myeloid neoplasm; 11 are in remission, 10 have persistent CLL/SLL, 15 died of CLL/SLL, and 1 died of adenocarcinoma.
Conclusions: We hypothesize that del(20q) resides in CLL/SLL cells, and is associated with atypical morphology, ZAP70 expression and unmutated IGHV genes. Following chemotherapy, CLL/SLL cells may acquire del(20q). Alternatively, chemotherapy may unmask a small resistant clone.
Monday, February 28, 2011 1:00 PM
Poster Session II # 172, Monday Afternoon