TCL1 Predicts Time to Treatment in Chronic Lymphocytic Leukemia
David P Ng, Reid R Bennett, Frederick Lansigan, Norman B Levy, Alexey V Danilov, Prabhjot Kaur. Dartmouth Hitchcock Medical Center, Lebanon, NH; Dartmouth Medical School, Hanover, NH
Background: Transgenic mice with T-cell leukemia 1 (TCL1) gene insertion have been shown to develop a lymphoproliferative disorder reminiscent of human B-CLL. TCL1 is aberrantly expressed in B-CLL and enhances NF-kB dependent transcription. A single study has shown that high TCL1 expression on peripheral blood CLL cells correlates with unmutated IgVH status. Here we report for the first time that TCL1 expression on bone marrow (BM) CLL lymphocytes predicts time-to-treatment (TTT).
Design: TCL1 expression was analyzed by immunohistochemistry in the BM trephine biopsies of 119 CLL patients, diagnosed between 2001 and 2010. Staining was graded by intensity (negative=0, weak=1, strong=2) and percentage of CLL cells positive (0-25%=0, 25-50%=1 and 50-100=2). These grades were added and a score of 3 or 4 considered TCL1 high. TCL1 expression was correlated with Rai stage at diagnosis, TTT, cytogenetic prognostic markers [good(13q), intermediate(normal or Trisomy12) and poor (17p, 11q, or complex)], and expression of CD38 and ZAP70. The data was analyzed using the logrank and chi-square tests.
Results: The mean age at diagnosis was 61±11.8 years. The M:F ratio was 3:2. The median follow up was 89 months (range, 5 – 299 months). Patients with low TCL1 expression exhibited longer time to treatment (80 months) compared with those with high expression (42 months) (p=0.046).
Higher TCL1 expression scores also correlated with higher Rai stage at diagnosis (p=0.018), and poorer cytogenetic prognostic markers (p=0.012). There was no correlation between TCL1 and ZAP-70 or CD38 expression.
Conclusions: Here we demonstrate that high TCL1 expression on CLL cells correlates with lower TTT, higher Rai stage, and may define a subset of CLL patients with a more aggressive clinical course. These findings, associated with recent animal data which implicates TCL1 in the pathogenesis of an animal model of CLL, suggest that TCL1 may have a role in the pathogenesis and prognosis of CLL.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 207, Monday Morning