Clinical and molecular characterization of patients with CLL
| Study rationale . | Patient No. . | CLL samples at time of disease onset (subgroups Prog-dt and Ind-dt) . | CLL samples during disease progression or after 4 y of follow-up (subgroups Prog-ddp and Ind-4years) . | TFT, months . | IgVH status‡ . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Binet stage . | LC, × 103/μl . | Clinical disease status . | FISH . | AID/LPL* . | CSR, %† . | Binet stage . | LC, × 103/μl . | Clinical disease status . | FISH . | AID/LPL* . | CSR, %† . | ||||
| Study cohort (progressive patients) | 1 | A | 19.0 | Ind. | Normal | (+/+) | 2.5 | B | 74.00 | Prog. | del17p | (+/+) | 2.0 | 18 | UM |
| 2 | A | 28.0 | Ind. | del11q | (+/+) | 2.1 | B | 162.0 | Prog. | del11q | (+/+) | 2.9 | 28 | UM | |
| 3 | A | 23.00 | Ind. | del13q/del11q | (+/+) | 2.8 | C | 120.0 | Prog. | del13q/del11q | (+/+) | 3.1 | 32 | UM | |
| 4 | A | 35.00 | Ind. | del11q | (+/+) | 4.1 | C | 164.0 | Prog. | del11q | (+/+) | 5.5 | 14 | UM | |
| 5 | A | 15.90 | Ind. | Normal | (+/+) | 3.8 | C | 220.0 | Prog. | Normal | (+/+) | 4.2 | 9 | UM | |
| Study cohort (indolent patients) | 6 | A | 27.70 | Ind. | Normal | (−/−) | 1.2 | A | 19.64 | Ind. | Normal | (−/−) | 0.9 | N/T | Mut |
| 7 | A | 24.60 | Ind. | Normal | (−/−) | 0.02 | A | 34.55 | Ind. | Normal | (−/−) | 0.5 | N/T | Mut | |
| 8 | A | 14.70 | Ind. | del13q | (−/−) | 1.1 | A | 12.50 | Ind. | del13q | (+/−) | 1.2 | N/T | Mut | |
| 9 | A | 8.25 | Ind. | del13q | (−/−) | 0.8 | A | 14 490 | Ind. | del13q | (−/−) | 0.3 | N/T | Mut | |
| 10 | A | 18.00 | Ind. | Normal | (−/−) | 1.5 | A | 20.00 | Ind. | Normal | (−/−) | 1.8 | N/T | Mut | |
| Validation cohort (progressive patients) | 11 | A | 26.20 | Ind. | del13q | (+/−) | 1.5 | C | 183.0 | Prog. | del13q | (+/−) | 2.2 | 33 | UM |
| 12 | A | 19.45 | Ind. | Normal | (−/+) | 0.5 | B | 112.0 | Prog. | del17p | (+/+) | 2.5 | 35 | UM | |
| 13 | A | 40.20 | Ind. | del13q | (+/+) | 1.2 | B | 98.00 | Prog. | del11q | (+/+) | 2.2 | 31 | UM | |
| 14 | A | 18.30 | Ind. | del13q/del11q | (+/+) | 1.6 | C | 178.00 | Prog. | del13q/del11q | (+/+) | 3.1 | 6 | UM | |
| 15 | A | 20.26 | Ind. | del17p | (−/+) | 1.8 | B | 154.00 | Prog. | del17p | (+/+) | 2.3 | 40 | UM | |
| 16 | A | 10.58 | Ind. | del11q | (+/+) | 0.5 | B | 120.0 | Prog. | del11q | (+/+) | 1.8 | 10 | UM | |
| 17 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | B | 77.00 | Prog. | del11q | (+/+) | 3.6 | 9 | UM | |
| 18 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | C | 161.00 | Prog. | del13q | (+/−) | 2.9 | 11 | UM | |
| 19 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | B | 72.0 | Prog. | del11q | (+/+) | 4.4 | 38 | UM | |
| 20 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | C | 900.0 | Prog. | Normal | (+/+) | 1.2 | 8 | UM | |
| 21 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | B | 110.0 | Prog. | del13q | (−/+) | 4.4 | 12 | UM | |
| 22 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | C | 97.00 | Prog. | Normal | (+/+) | 2.5 | 26 | UM | |
| 23 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | B | 65.00 | Prog. | Normal | (+/+) | 1.5 | 24 | UM | |
| Validation cohort (indolent patients) | 24 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 15.60 | Ind. | Normal | (−/+) | 0.6 | 130 | Mut |
| 25 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 8.90 | Ind. | tris12 | (−/−) | 0.5 | N/T | Mut | |
| 26 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 9.92 | Ind. | Normal | (−/−) | 0.07 | N/T | Mut | |
| 27 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 15.00 | Ind. | Normal | (−/−) | 0.05 | N/T | Mut | |
| 28 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 7.00 | Ind. | del13q | (−/+) | 1.5 | N/T | Mut | |
| 29 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 11.60 | Ind. | del13q | (+/−) | 1.1 | N/T | Mut | |
| 30 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 14.70 | Ind. | tri12 | (−/−) | 2.1 | 126 | Mut | |
| 31 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 22.20 | Ind. | Normal | (−/+) | 1.8 | N/T | Mut | |
| 32 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 11.60 | Ind. | Normal | (−/−) | 0.6 | N/T | Mut | |
| 33 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 17.50 | Ind. | Normal | (−/−) | 0.7 | N/T | Mut | |
| 34 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 19.90 | Ind. | del13q | (−/−) | 1.1 | N/T | Mut | |
| Study rationale . | Patient No. . | CLL samples at time of disease onset (subgroups Prog-dt and Ind-dt) . | CLL samples during disease progression or after 4 y of follow-up (subgroups Prog-ddp and Ind-4years) . | TFT, months . | IgVH status‡ . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Binet stage . | LC, × 103/μl . | Clinical disease status . | FISH . | AID/LPL* . | CSR, %† . | Binet stage . | LC, × 103/μl . | Clinical disease status . | FISH . | AID/LPL* . | CSR, %† . | ||||
| Study cohort (progressive patients) | 1 | A | 19.0 | Ind. | Normal | (+/+) | 2.5 | B | 74.00 | Prog. | del17p | (+/+) | 2.0 | 18 | UM |
| 2 | A | 28.0 | Ind. | del11q | (+/+) | 2.1 | B | 162.0 | Prog. | del11q | (+/+) | 2.9 | 28 | UM | |
| 3 | A | 23.00 | Ind. | del13q/del11q | (+/+) | 2.8 | C | 120.0 | Prog. | del13q/del11q | (+/+) | 3.1 | 32 | UM | |
| 4 | A | 35.00 | Ind. | del11q | (+/+) | 4.1 | C | 164.0 | Prog. | del11q | (+/+) | 5.5 | 14 | UM | |
| 5 | A | 15.90 | Ind. | Normal | (+/+) | 3.8 | C | 220.0 | Prog. | Normal | (+/+) | 4.2 | 9 | UM | |
| Study cohort (indolent patients) | 6 | A | 27.70 | Ind. | Normal | (−/−) | 1.2 | A | 19.64 | Ind. | Normal | (−/−) | 0.9 | N/T | Mut |
| 7 | A | 24.60 | Ind. | Normal | (−/−) | 0.02 | A | 34.55 | Ind. | Normal | (−/−) | 0.5 | N/T | Mut | |
| 8 | A | 14.70 | Ind. | del13q | (−/−) | 1.1 | A | 12.50 | Ind. | del13q | (+/−) | 1.2 | N/T | Mut | |
| 9 | A | 8.25 | Ind. | del13q | (−/−) | 0.8 | A | 14 490 | Ind. | del13q | (−/−) | 0.3 | N/T | Mut | |
| 10 | A | 18.00 | Ind. | Normal | (−/−) | 1.5 | A | 20.00 | Ind. | Normal | (−/−) | 1.8 | N/T | Mut | |
| Validation cohort (progressive patients) | 11 | A | 26.20 | Ind. | del13q | (+/−) | 1.5 | C | 183.0 | Prog. | del13q | (+/−) | 2.2 | 33 | UM |
| 12 | A | 19.45 | Ind. | Normal | (−/+) | 0.5 | B | 112.0 | Prog. | del17p | (+/+) | 2.5 | 35 | UM | |
| 13 | A | 40.20 | Ind. | del13q | (+/+) | 1.2 | B | 98.00 | Prog. | del11q | (+/+) | 2.2 | 31 | UM | |
| 14 | A | 18.30 | Ind. | del13q/del11q | (+/+) | 1.6 | C | 178.00 | Prog. | del13q/del11q | (+/+) | 3.1 | 6 | UM | |
| 15 | A | 20.26 | Ind. | del17p | (−/+) | 1.8 | B | 154.00 | Prog. | del17p | (+/+) | 2.3 | 40 | UM | |
| 16 | A | 10.58 | Ind. | del11q | (+/+) | 0.5 | B | 120.0 | Prog. | del11q | (+/+) | 1.8 | 10 | UM | |
| 17 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | B | 77.00 | Prog. | del11q | (+/+) | 3.6 | 9 | UM | |
| 18 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | C | 161.00 | Prog. | del13q | (+/−) | 2.9 | 11 | UM | |
| 19 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | B | 72.0 | Prog. | del11q | (+/+) | 4.4 | 38 | UM | |
| 20 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | C | 900.0 | Prog. | Normal | (+/+) | 1.2 | 8 | UM | |
| 21 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | B | 110.0 | Prog. | del13q | (−/+) | 4.4 | 12 | UM | |
| 22 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | C | 97.00 | Prog. | Normal | (+/+) | 2.5 | 26 | UM | |
| 23 | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | N/A(1) | B | 65.00 | Prog. | Normal | (+/+) | 1.5 | 24 | UM | |
| Validation cohort (indolent patients) | 24 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 15.60 | Ind. | Normal | (−/+) | 0.6 | 130 | Mut |
| 25 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 8.90 | Ind. | tris12 | (−/−) | 0.5 | N/T | Mut | |
| 26 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 9.92 | Ind. | Normal | (−/−) | 0.07 | N/T | Mut | |
| 27 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 15.00 | Ind. | Normal | (−/−) | 0.05 | N/T | Mut | |
| 28 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 7.00 | Ind. | del13q | (−/+) | 1.5 | N/T | Mut | |
| 29 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 11.60 | Ind. | del13q | (+/−) | 1.1 | N/T | Mut | |
| 30 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 14.70 | Ind. | tri12 | (−/−) | 2.1 | 126 | Mut | |
| 31 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 22.20 | Ind. | Normal | (−/+) | 1.8 | N/T | Mut | |
| 32 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 11.60 | Ind. | Normal | (−/−) | 0.6 | N/T | Mut | |
| 33 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 17.50 | Ind. | Normal | (−/−) | 0.7 | N/T | Mut | |
| 34 | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | N/A(2) | A | 19.90 | Ind. | del13q | (−/−) | 1.1 | N/T | Mut | |
AID, activation-induced cytidine deaminase; CSR, class-switch recombination; FISH, fluorescence in situ hybridization; LC, lymphocyte count; LPL, lipoprotein lipase; Mut, mutated; N/A(1), not applicable (refers to patients with progressive disease whose samples were not collected at disease onset); N/A(2), not applicable (refers to analyzed samples collected from indolent patients after 4 years of follow-up); N/T, not treated (refers to patients who did not receive any treatment at 4-year follow-up); TFT, time from initial diagnosis to first treatment for clinical progression; UM, unmutated.
AID and LPL expression were assessed by quantitative polymerase chain reaction, as described by Prieto et al.21
Percentage of proliferative fraction expressing IgM+/IgG+ evaluated by cytometry studies, as described by Palacios et al.14
≤ 2% difference from germline gene defined UM patients; ≥ 2% difference defined Mut patients.