Molecular Cytogenetics Analysis of 13q14 Biallelic Deletion in Chronic Lymphocytic Leukemia: A Study on 250 Patients
Authors: Gozzetti Alessandro , Papini Giulia , Crupi Rosaria , Frasconi Adele , Forconi Francesco , Cencini Emanuele , Raspadori Donatella , Lauria Francesco 
Published: October 2019

Abstract
Abstract 1454
Deletion 13q14 (13q-) detected by fluorescence in situ hybridization (FISH) is the most frequent chromosomal abnormality in chronic lymphocytic leukemia (CLL). When 13q- is detected as sole abnormality has a good prognosis, while aggressive outcome is registered when 13q- is combined with other chromosomal abnormalities such as del 11q or del 17p. A recent study evidenced also that patients with higher percentage of 13q-deleted cells (>70%) are at higher risk for aggressive disease. Some studies evidenced that 13q- deletion size (involving D13S319 +/−Rb1) seems to matter in terms of time to treatment (TTT) and prognosis (OS). Few studies evaluated so far the incidence and prognosis of a biallelic 13q- deletion, i.e. the deletion of both alleles of the minimal deleted region (MDR) of chromosome 13q.In particular prognosis has been reported controversial. We analyzed at single institution 250 CLL patients by FISH in order to evaluate the incidence and prognosis of biallelic 13q- by using probes for D13S319 and RB1 that map to DLEU2/MIR15A/MIR16-1 and RB1 loci. Results were correlated in terms of TTT and OS with IGHV mutational status (mutated vs unmutated), RAI/BINET stage, CD38 positivity and/ or ZAP-70 positivity, beta-2M, LDH, other chromosomal abnormality (+12, del17p, del11q). Deletion 13q was considered present if >10% of nuclei were deleted out of 300 nuclei scored by two different and independent observers. All biallelic cases were confirmed by FISH using a probe for LSI-D13S319 and 13q34 to exclude false positive results. 135/250 (52%) patients presented a monoallelic del 13q. 45/135 (32%) presented a monoallelic del of RB1 while 20/135 (15%) cases presented a biallelic 13q-.12/20 (80%) presented a biallelic 13q- as sole abnormality, while 8/20 presented a 13q- associated with other cytogenetic abnormalities (one 17p-, five 11q-, two +12). The median percentage of 13q-deleted cells was 50% (range 14–86). Median age was 65 (range 50–85), M/F 12/8; 80% of the patients were RAI stage 0–1, while only 10% were RAI stage 4. No differences were seen in patients with biallelic deletion of 13q when LDH, b2M, ZAP-70,IGHV were considered. CD38 was negative in 16/20 patients. Regarding the MDR of chromosome 13q, 11/20 patients presented a biallelic del of D13S319, while 5/20 had a biallelic deletion of RB1; 5/20 patients presented a mono+biallelic del of D13S319 while 3/20 a mono+biallelic deletion of RB1. When we analyzed clinical and biological characteristics comparing patients with biallelic13q-,monoallelic 13q- and with no 13q-, we did not find differences in terms of: stage (RAI-Binet), P=0.2,P=0.9; B2 M, P=0.4; LDH,P=0.1; CD38 positivity, P=0.2; ZAP-70, P=0,1; IGHV M vs UM,P=0.65; P53 mutated vs wild type, P=0.1; del 11q was significantly associated more with biallelic 13q-, P=0.02. TTT and OS were not significantly different between biallelic 13q- patients and the other two groups (164 vs 212 vs 211, P=0.9). 8/20 patients with biallelic 13q- have been treated, all 5 patients carrying also a 11q- received treatment, the other 3 patients had: 1patient RB1 deletion in 92% of cells and 2 deletion 13q- in>75% of cells. In conclusion, biallelic 13q- are present in about 8% of all cases of CLL and in 15% of 13q- patients. A strong association with del 11q was found and this correlated with disease progression and treatment.CD38 was negative in the majority of patients with biallelic 13q-. RB1 was deleted in 32% of 13q- patients. No differences were found in terms of clinical characteristics, TTT and OS with monoallelic 13q-.

Disclosures:
No relevant conflicts of interest to declare.