The Prognostic Significance of 13q Deletion with Different Size in Patients with B-CLPD

Background: Deletion of 13q14 is the most frequent abnormality in chronic lymphocytic leukemia (CLL). Deletion at of 13q with vary sizes have been described, documenting different involved genes with different deletion area. But the prognostic significance of different deletion size is not well explored and this interesting phenomenon has not been described in other B-cell chronic lymphoproliferative disorders (B-CLPD).

Patients and Methods: Interphase fluorescence in situ hybridization (FISH) using locus-specific probes (RB1, D13S25) was performed to detect 13q14 deletions on 344 untreated cases with B-CLPD, including 304 CLL patients and 166 other B-CLPD patients. Different 13q14 deletion area was delineated by RB1 and D13S25.

Results: (a) Totally, 145 of 304 CLL patients (47.9%) had 13q14 deletion, which was significantly higher than it in other B-CLPD (25/167, 15.0%; p=.000). 77 of 304 CLL patients (25.3%) and 14 of 166 other B-CLPD patients (8.4%) had RB1 deletion. RB1 deletion always accompanied with D13S25 deletion in both CLL and other B-CLPD, which indicated large area deletion in 13q14. But some patients had only D13S25 deletion without RB1 deletion, indicating small area deletion in 13q14. Of the 145 CLL cases with 13q14 deletion, 73(50.3%) had small deletion and 72 (49.7%) with large deletion. The incidence of small and large deletion in 21 other B-CLPD with 13q14 deletion were in 12(48.0%) and 113(52.0%) patients respectively.

(b) In CLL cases, the time to first therapy in the cases with 13q14 deletion was 25 months longer than 16 months in the cases without 13q14 deletion (P=0.035). The progression-free survival (PFS) in cases with 13q14 deletion was also significantly longer (P=0.023) than those without the aberration. In other B-CLPD cases, the PFS and OS in cases with 13q14 deletion was significantly shorter (P=0.030) than those without the aberration. Moreover, large deletions (from RB1 to D13S25) were associated with a significantly shorter (p< 0.05) TFT as well as overall survival (57.5 vs. 135.0 months, p=.075)compared with small deletions.

Conclusions: The deletion of 13q can influence clinical outcome of BCLPD and vary in size both in CLL and in other BCLPDs. The deletion size displayed as a poor prognostic factor in other BCLPD cases, which implies the usage of both 13q probes is proposed.