A higher percentage of cells with 13q deletion predicts worse outcome in Chinese patients with chronic lymphocytic leukemia carrying isolated 13q deletion

Abstract

Previous studies showed that, in chronic lymphocytic leukemia (CLL) patients with isolated 13q deletion (13q-), those carrying higher percentage of leukemic cells with 13q- had more aggressive diseases. However, the prognostic value of the percentage of leukemic cells with 13q- in Chinese CLL patients with isolated 13q- remained to be determined. Using interphase fluorescence in situ hybridization (FISH), we identified 82 patients (25.4%) with isolated 13q deletion from a cohort of 323 untreated CLL patients. Among patients with isolated 13q deletion, cases of 13q- cells ≥ 80% (13q-H) had significantly shorter time to first treatment (TTT) than those of < 80% 13q- cells (13q-L) (median 11 vs. 92 months, p = 0.0016). A higher lymphocyte count (p = 0.0650) was associated with 13q-H, while other clinical, immunophenotypic, or molecular features did not differ between patients with 13q-H and 13q-L. Although 13q-H only showed marginal significance in multivariate analysis of TTT (hazards ratio 2.007; 95% confidence interval 0.975-4.129; p = 0.059), it helped refine the risk stratification based on Binet stage or immunoglobulin heavy chain variable gene (IGHV) status. In cases in Binet A or B stage, patients with 13q-H had a significantly shorter TTT (median TTT 18 months vs. undefined, p = 0.0101). And in IGHV mutated patients, 13q-H was also associated with reduced TTT (median TTT 13q-H. 18 months vs. 13q-L undefined, p = 0.0163). In conclusion, the prognosis of CLL patients with isolated 13q deletion was heterogeneous with 13q-H identifying patients with worse outcome.

Low prevalence and independent prognostic role of del(11q) in Chinese patients with chronic lymphocytic leukemia

“…We used peripheral blood/bone marrow samples to detect cytogenetic, molecular, and immunophenotypic aberrations. FISH was conducted to detect del(17p), del(11q), del(13q), and trisomy 12 according to the procedures described previously [20] . FISH probes included: LSI D13S319 for detection of del(13q14), LSI ATM for detection of del(11q22.3), CEP12 (centromere 12) for detection of trisomy 12 and LSI p53 for detection of del(17p13).…”

Analyzing The Mutations Of Notch1 And Sf3b1 Genes In Cases With CLL Detected Isolated 13q Deletion

“…CLL patients with isolated 13q deletion have better prognosis than CLL patients with nonisolated del(13q). However, it is known that CLL patients with isolated del(13q) have heterogeneity in terms of prognosis (OS, TTFT) (6). It is suggested that the reason behind this heterogeneity, may be the size of the 13q deletion, deletion rate and additional gene mutations.…”

“…In addition, the rate of mutation detected in the SF3B1 gene in cases with non-isolated 13q deletion was reported as 0% and the rate of mutation in the relevant gene in isolated del(13q) cases was reported as 4.8%. The researchers stated that the mutations of the genes were associated with high del(13q) ratio (> 80%) (6). Although the deletion rate of 13q was > 80% in the case with detected NOTCH1 gene mutation, no mutation was detected in the other 9 cases with > 80% deletion rate.…”

98% IGHV gene identity is the optimal cutoff to dichotomize the prognosis of Chinese patients with chronic lymphocytic leukemia

“…We performed interphase fluorescence in situ hybridization (FISH) of del(11q22.3), del(17p13), del (13q14), and trisomy 12 and Sanger sequencings of TP53 (exon 4‐9), NOTCH1 (PEST domain), SF3B1 (exon 14‐16), and MYD88 (exon 3‐5), as described previously …”