Subsets of CLL cases of the present series with stereotyped HCDR3 sequences. The asterisks denote previously published subsets
| Set . | N . | IGHV gene† . | IGHD gene‡ (reading frame) . | IGHJ gene§ . | Average Intra-subset homology‖ . | IGKV/IGLV gene (no. cases with indicated gene/total no. cases with available data) . |
|---|---|---|---|---|---|---|
| Confirmed subsets | ||||||
| 1* | 20 | IGHV1-18 (4), IGHV1-2 (4), IGHV1-3 (8), IGHV5-a (3) | IGHD6-19 (3) | IGHJ4 | 71.2 | IGKV1-39/IGKV1D-39 (15/15) |
| 2* | 18 | IGHV3-21 (16), IGHV3-11 (1), IGHV3-48 (1) | ND | IGHJ6 | 85.2 | IGLV3-21 (15/17) |
| 3* | 12 | IGHV1-69 (9), IGHV1-2 (1), IGHV1-8 (1), IGHV4-34 (1) | IGHD2-2 (3) | IGHJ6 | 82.2 | IGKV1-39/IGKV1D-39 (3/9), IGKV3-11 (3/9) |
| 4* | 13 | IGHV4-34 | IGHD5-5 (1)/D4-17 (3) | IGHJ6 | 75.4 | IGKV2-30 (11/11) |
| 5* | 10 | IGHV1-69 | IGHD3-10 (3) | IGHJ6 | 78.3 | IGKV1-33/IGKV1D-33 (2/7), IGLV3-21 (2/7) |
| 6* | 8 | IGHV1-69 | IGHD3-16 (2) | IGHJ3 | 92.3 | IGKV3-20 (6/8) |
| 7* | 8 | IGHV1-69 | IGHD3-3 (2) | IGHJ6 | 64.8 | IGLV3-9 (2/6) |
| 8* | 7 | IGHV4-39 | IGHD6-13 (1) | IGHJ5 | 69.9 | IGKV1-39/IGKV1D-39 (6/7) |
| 9 | 7 | IGHV1-69 (4), IGHV3-21 (1), IGHV3-23 (1), IGHV3-30 (1) | IGHD3-3 (3) | IGHJ6 | 76.4 | diverse |
| 10 | 5 | IGHV4-39 (4), IGHV2-5 (1) | IGHD2-2 (2) | IGHJ6 | 74.4 | IGLV1-40 (2/5), IGLV1-51 (2/5) |
| 11 | 4 | IGHV4-34 (3), IGHV4-59 (1) | IGHD3-10 (2) | IGHJ4 | 68.3 | IGKV3-20 (2/2) |
| 12 | 4 | IGHV1-2 (3), IGHV1-46 (1) | IGHD3-22 (2) | IGHJ4 | 76.1 | IGKV3-15 (3/3) |
| 13 | 3 | IGHV4-59 | IGHD2-15 (2) | IGHJ2 | 90.7 | IGKV3-20 (3/3) |
| 14 | 3 | IGHV4-4 | IGHD2-21 (2) | IGHJ4 | 76.7 | diverse |
| 15 | 3 | IGHV1-69 | IGHD5-24 (1) | IGHJ3 | 74.5 | IGKV3-20 (2/2) |
| 16 | 3 | IGHV4-34 | IGHD2-15 (2) | IGHJ6 | 70.8 | diverse |
| 17 | 3 | IGHV3-23 (1), IGHV3-33 (1), IGHV3-7 (1) | IGHD4-23 (2) | IGHJ4 | 77.1 | diverse |
| 18 | 3 | IGHV3-23 (1), IGHV3-48(1), IGHV3-11 (1) | IGHD4-23 (2) | IGHJ3 | 84.6 | NA |
| 19 | 3 | IGHV1-69 (2), IGHV3-74 (1) | IGHD3-9 (2) | IGHJ4 | 65.1 | NA |
| 20 | 3 | IGHV3-53 | ND | IGHJ4 | 60.6 | IGLV3-21 (3/3) |
| 21 | 3 | IGHV3-11 (1), IGHV3-23 (2) | IGHD3-3 (2) | IGHJ6 | 64.3 | IGLV1-44/47 (2/2) |
| 22 | 3 | IGHV3-23 (1), IGHV3-21 (1), IGHV3-11 (1) | IGHD3-3 (2) | IGHJ6 | 76.2 | NA |
| 23 | 3 | IGHV3-30 (1), IGHV3-15 (1), IGHV3-66 (1) | IGHD3-9 (1) | IGHJ6 | 71.2 | diverse |
| 24 | 3 | IGHV1-2 (2), IGHV4-4 (1) | IGHD2-2 (2) | IGHJ6 | 70.4 | diverse |
| 25 | 3 | IGHV1-8 (1), IGHV3-11 (2) | IGHD3-3 (1) | IGHJ6 | 70.8 | diverse |
| 26 | 3 | IGHV4-b (1), IGHV1-69 (1), IGHV3-66 (1) | IGHD6-13 (1) | IGHJ6 | 80 | NA |
| Subsets confirmed by public database cell sequences from other group¶ | ||||||
| 27 | 2 | IGHV1-69 | IGHD3-22 (2) | IGHJ4 | 75 | NA |
| 28* | 2 | IGHV1-2 | IGHD1-26 (1) | IGHJ6 | 88.2 | IGKV4-1 (2/2) |
| 29 | 2 | IGHV4-34 | IGHD6-19 (2) | IGHJ3 | 85.7 | NA |
| 30 | 2 | IGHV3-9 | IGHD3-3 (2) | IGHJ4 | 94.7 | IGKV3-20 (2/2) |
| 31 | 2 | IGHV3-48 | IGHD3-3 (2) | IGHJ6 | 80.9 | IGLV1-44 (2/2) |
| 32 | 2 | IGHV3-48 | IGHD3-22 (2) | IGHJ6 | 80 | NA |
| 33 | 2 | IGHV4-39 | IGHD3-22 (2) | IGHJ4 | 70.6 | IGKV3-11 (2/2) |
| 34 | 2 | IGHV1-69 (1), IGHV1-18 (1) | IGHD3-9 (2) | IGHJ6 | 69.2 | NA |
| 35 | 2 | IGHV1-69 (1), IGHV3-21 (1) | IGHD3-22 (2) | IGHJ6 | 76 | diverse |
| Potential subsets | ||||||
| 36 | 2 | IGHV3-30 | IGHD3-3 (2) | IGHJ4 | 91.7 | IGKV2-28/2D-28 (2/2) |
| 37* | 2 | IGHV4-b | IGHD6-13 (1) | IGHJ4 | 60 | IGLV1-44 (2/2) |
| 38 | 2 | IGHV4-39 (2), IGHV4-59 (1) | IGHD3-3 (2) | IGHJ5 | 61 | IGKV1-33/IGKV1D-33 (2/2) |
| 39 | 2 | IGHV3-1 | IGHD3-16 (3) | IGHJ1 | 64.3 | NA |
| 40 | 2 | IGHV3-33 (1), IGHV3-30 (1) | IGHD1-26 (1) | IGHJ4 | 100 | NA |
| 41 | 2 | IGHV3-21 (1), IGHV3-48 (1) | IGHD2-2 (2) | IGHJ6 | 79.2 | diverse |
| 42 | 2 | IGHV2-70 | IGHD3-10 (2) | IGHJ4 | 68.7 | NA |
| 43 | 2 | IGHV3-33 | IGHD2-15 (2) | IGHJ5 | 65.2 | diverse |
| 44 | 2 | IGHV3-48 | IGHD4-23 (3) | IGHJ6 | 65 | NA |
| 45 | 2 | IGHV4-39 | IGHD3-22 (2) | IGHJ5 | 63.2 | diverse |
| 46 | 2 | IGHV4-b (1), IGHV3-23 (1) | IGHD6-19 (1) | IGHJ4 | 71.4 | diverse |
| 47 | 2 | IGHV3-66 | IGHD2-15 (2) | IGHJ5 | 78.6 | diverse |
| 48 | 2 | IGHV3-74 (1), IGHV3-15 (1) | IGHD4-17 (2) | IGHJ4 | 66.7 | NA |
| Set . | N . | IGHV gene† . | IGHD gene‡ (reading frame) . | IGHJ gene§ . | Average Intra-subset homology‖ . | IGKV/IGLV gene (no. cases with indicated gene/total no. cases with available data) . |
|---|---|---|---|---|---|---|
| Confirmed subsets | ||||||
| 1* | 20 | IGHV1-18 (4), IGHV1-2 (4), IGHV1-3 (8), IGHV5-a (3) | IGHD6-19 (3) | IGHJ4 | 71.2 | IGKV1-39/IGKV1D-39 (15/15) |
| 2* | 18 | IGHV3-21 (16), IGHV3-11 (1), IGHV3-48 (1) | ND | IGHJ6 | 85.2 | IGLV3-21 (15/17) |
| 3* | 12 | IGHV1-69 (9), IGHV1-2 (1), IGHV1-8 (1), IGHV4-34 (1) | IGHD2-2 (3) | IGHJ6 | 82.2 | IGKV1-39/IGKV1D-39 (3/9), IGKV3-11 (3/9) |
| 4* | 13 | IGHV4-34 | IGHD5-5 (1)/D4-17 (3) | IGHJ6 | 75.4 | IGKV2-30 (11/11) |
| 5* | 10 | IGHV1-69 | IGHD3-10 (3) | IGHJ6 | 78.3 | IGKV1-33/IGKV1D-33 (2/7), IGLV3-21 (2/7) |
| 6* | 8 | IGHV1-69 | IGHD3-16 (2) | IGHJ3 | 92.3 | IGKV3-20 (6/8) |
| 7* | 8 | IGHV1-69 | IGHD3-3 (2) | IGHJ6 | 64.8 | IGLV3-9 (2/6) |
| 8* | 7 | IGHV4-39 | IGHD6-13 (1) | IGHJ5 | 69.9 | IGKV1-39/IGKV1D-39 (6/7) |
| 9 | 7 | IGHV1-69 (4), IGHV3-21 (1), IGHV3-23 (1), IGHV3-30 (1) | IGHD3-3 (3) | IGHJ6 | 76.4 | diverse |
| 10 | 5 | IGHV4-39 (4), IGHV2-5 (1) | IGHD2-2 (2) | IGHJ6 | 74.4 | IGLV1-40 (2/5), IGLV1-51 (2/5) |
| 11 | 4 | IGHV4-34 (3), IGHV4-59 (1) | IGHD3-10 (2) | IGHJ4 | 68.3 | IGKV3-20 (2/2) |
| 12 | 4 | IGHV1-2 (3), IGHV1-46 (1) | IGHD3-22 (2) | IGHJ4 | 76.1 | IGKV3-15 (3/3) |
| 13 | 3 | IGHV4-59 | IGHD2-15 (2) | IGHJ2 | 90.7 | IGKV3-20 (3/3) |
| 14 | 3 | IGHV4-4 | IGHD2-21 (2) | IGHJ4 | 76.7 | diverse |
| 15 | 3 | IGHV1-69 | IGHD5-24 (1) | IGHJ3 | 74.5 | IGKV3-20 (2/2) |
| 16 | 3 | IGHV4-34 | IGHD2-15 (2) | IGHJ6 | 70.8 | diverse |
| 17 | 3 | IGHV3-23 (1), IGHV3-33 (1), IGHV3-7 (1) | IGHD4-23 (2) | IGHJ4 | 77.1 | diverse |
| 18 | 3 | IGHV3-23 (1), IGHV3-48(1), IGHV3-11 (1) | IGHD4-23 (2) | IGHJ3 | 84.6 | NA |
| 19 | 3 | IGHV1-69 (2), IGHV3-74 (1) | IGHD3-9 (2) | IGHJ4 | 65.1 | NA |
| 20 | 3 | IGHV3-53 | ND | IGHJ4 | 60.6 | IGLV3-21 (3/3) |
| 21 | 3 | IGHV3-11 (1), IGHV3-23 (2) | IGHD3-3 (2) | IGHJ6 | 64.3 | IGLV1-44/47 (2/2) |
| 22 | 3 | IGHV3-23 (1), IGHV3-21 (1), IGHV3-11 (1) | IGHD3-3 (2) | IGHJ6 | 76.2 | NA |
| 23 | 3 | IGHV3-30 (1), IGHV3-15 (1), IGHV3-66 (1) | IGHD3-9 (1) | IGHJ6 | 71.2 | diverse |
| 24 | 3 | IGHV1-2 (2), IGHV4-4 (1) | IGHD2-2 (2) | IGHJ6 | 70.4 | diverse |
| 25 | 3 | IGHV1-8 (1), IGHV3-11 (2) | IGHD3-3 (1) | IGHJ6 | 70.8 | diverse |
| 26 | 3 | IGHV4-b (1), IGHV1-69 (1), IGHV3-66 (1) | IGHD6-13 (1) | IGHJ6 | 80 | NA |
| Subsets confirmed by public database cell sequences from other group¶ | ||||||
| 27 | 2 | IGHV1-69 | IGHD3-22 (2) | IGHJ4 | 75 | NA |
| 28* | 2 | IGHV1-2 | IGHD1-26 (1) | IGHJ6 | 88.2 | IGKV4-1 (2/2) |
| 29 | 2 | IGHV4-34 | IGHD6-19 (2) | IGHJ3 | 85.7 | NA |
| 30 | 2 | IGHV3-9 | IGHD3-3 (2) | IGHJ4 | 94.7 | IGKV3-20 (2/2) |
| 31 | 2 | IGHV3-48 | IGHD3-3 (2) | IGHJ6 | 80.9 | IGLV1-44 (2/2) |
| 32 | 2 | IGHV3-48 | IGHD3-22 (2) | IGHJ6 | 80 | NA |
| 33 | 2 | IGHV4-39 | IGHD3-22 (2) | IGHJ4 | 70.6 | IGKV3-11 (2/2) |
| 34 | 2 | IGHV1-69 (1), IGHV1-18 (1) | IGHD3-9 (2) | IGHJ6 | 69.2 | NA |
| 35 | 2 | IGHV1-69 (1), IGHV3-21 (1) | IGHD3-22 (2) | IGHJ6 | 76 | diverse |
| Potential subsets | ||||||
| 36 | 2 | IGHV3-30 | IGHD3-3 (2) | IGHJ4 | 91.7 | IGKV2-28/2D-28 (2/2) |
| 37* | 2 | IGHV4-b | IGHD6-13 (1) | IGHJ4 | 60 | IGLV1-44 (2/2) |
| 38 | 2 | IGHV4-39 (2), IGHV4-59 (1) | IGHD3-3 (2) | IGHJ5 | 61 | IGKV1-33/IGKV1D-33 (2/2) |
| 39 | 2 | IGHV3-1 | IGHD3-16 (3) | IGHJ1 | 64.3 | NA |
| 40 | 2 | IGHV3-33 (1), IGHV3-30 (1) | IGHD1-26 (1) | IGHJ4 | 100 | NA |
| 41 | 2 | IGHV3-21 (1), IGHV3-48 (1) | IGHD2-2 (2) | IGHJ6 | 79.2 | diverse |
| 42 | 2 | IGHV2-70 | IGHD3-10 (2) | IGHJ4 | 68.7 | NA |
| 43 | 2 | IGHV3-33 | IGHD2-15 (2) | IGHJ5 | 65.2 | diverse |
| 44 | 2 | IGHV3-48 | IGHD4-23 (3) | IGHJ6 | 65 | NA |
| 45 | 2 | IGHV4-39 | IGHD3-22 (2) | IGHJ5 | 63.2 | diverse |
| 46 | 2 | IGHV4-b (1), IGHV3-23 (1) | IGHD6-19 (1) | IGHJ4 | 71.4 | diverse |
| 47 | 2 | IGHV3-66 | IGHD2-15 (2) | IGHJ5 | 78.6 | diverse |
| 48 | 2 | IGHV3-74 (1), IGHV3-15 (1) | IGHD4-17 (2) | IGHJ4 | 66.7 | NA |
N indicates number of cases; ND, not determined; NA, not available.
Previously published subsets.
The relative frequencies of stereotyped HCDR3s were significantly different among rearrangements using IGHV1 versus IGHV3 versus IGHV4 subgroup genes (34% versus 15% versus 23%; P < .001).
An increased frequency of IGHD6 subgroup genes (P = .05) as well as a decreased frequency of IGHD1 subgroup genes (P < .01) was observed among stereotyped HCDR3 cases.
IGHJ4 was found at a decreased frequency and IGHJ6 at an increased frequency in rearrangements with stereotyped HCDR3s (29% versus 53%, respectively; P < .01).
The percentage of HCDR3 amino acid identity was evaluated pair-wise for all members of a subset and used to calculate the average intra-subset HCDR3 homology. In the case of subset nos. 34 and 40, some pairs of sequences had >55% but <60% amino acid identity; however, different amino acids often shared similar properties. Furthermore, both subsets were characterized by restricted light-chain usage and CDR3.
HCDR3 public-database CLL sequences from other groups that “confirmed” the existence of subsets of the present series with two members only are shown in Figure 1 and in Tables S5-S6.