Concomitant heterochromatinisation and down-regulation of gene expression unveils epigenetic silencing of RELBin an aggressive subset of chronic lymphocytic leukemia in males

Table 1 Clinical characteristics and outcomes of CLL patients

Patient's ID	Sex	Age (years)	Binet's stage	FISH Aberrations	Treatment	Matutes	sCD23 PVT	Apoptosis in vitro
B118R	Male	89	A	del(13q14) biallelic; del(11q22)monoallelic	yes	5	160	Resistant
G151R	Male	56	A	del(13q14)biallelic	yes	5	ND	Resistant
E147R	Male	70	A	del(13q14)biallelic; del(17p13)monoallelic	yes	4	ND	Resistant
B138R	Male	65	A	del(13q14)monoallelic	yes	5	ND	Resistant
RM1	Male	81	A	del(13q14)biallelic; del(17p13)monoallelic	yes	5	105	Resistant
RM2	Male	77	A	del(13q14)biallelic	yes	5	400	Resistant
RM3	Male	56	A	del(13q14)monoallelic	yes	4	102	Resistant
RF1	Female	74	A	del(13q14)biallelic; del(17p13)monoallelic	yes	5	443	Resistant
RF2	Female	67	A	del(13q14)monoallelic; del(17p13)monoallelic	yes	5	72	Resistant
RF3	Female	56	A	del(13q14)biallelic; del(17p13)monoallelic	no	5	ND	Resistant
U231R	Female	76	A	del(13q14)monoallelic	yes	5	ND	Resistant
G244S	Female	63	A	del(13q14)monoallelic; del(17p13)monoallelic	no	5	ND	Sensitive
B229S	Female	78	A	del(13q14)monoallelic	no	5	ND	Sensitive
S240S	Female	67	A	no	no	4	ND	Sensitive
SF1	Female	80	A	ND	no	4	70	Sensitive
SF2	Female	62	A	ND	no	4	28	Sensitive
SF3	Female	84	A	ND	no	5	97	Sensitive
SM1	Male	82	A	ND	no	4	52	Sensitive
SM2	Male	65	A	no	no	5	high	Sensitive
SM3	Male	74	A	del(13q14)monoallelic	no	4	low	Sensitive
L130S	Male	77	A	del(13q14)monoallelic	no	4	ND	Sensitive
S152S	Male	77	A	ND	no	4	458	Sensitive
B130S	Male	77	A	del(13q14)monoallelic	yes	4	93	Sensitive
B118S	Male	89	A	del(11q22) monoallelic	yes	4	160	Sensitive
M124S	Male	83	A	ND	no	5	ND	Sensitive

Apoptosis score was established 24 h after cell exposure to 10 Gy of γ-rays. Patients were considered sensitive (S) when the number of apoptotic cells was at least twofold higher in irradiated cells than in non-irradiated at 24 h of cell culture, or as resistant (R) when no difference was observed between irradiated and non-irradiated cells. Patients RM2 and B118S/R shifted from S to R status. Matutes scoring system was established to distinguish CLL from other lymphoproliferative disorders. This score is based on the immunophenotypic analysis of five markers: CD5⁺, CD23⁺, FMC7^- and CD79b^-, weak expression of monotypic κ or λ light chain. A value of 1 is assigned to a given marker with a level typical of CLL, and a total Matutes score at 4 or 5 indicates diagnosis of typical CLL. ND, not determined. Chromosomal aberrations were established by FISH using LSI ATM/LSI p53 and LSI D13S319/LSI 13q34/CEP12 probe sets (Abbott, France) which are complementary to 11q22.3, 17p13.1, 13q14.3, 13q34 and 12p11.1-q11 genome regions, respectively. To be taken into account, the aberration should be present in at least 5% of nuclei.

ISSN: 1755-8794