Genetically inspired mouse models of CLL and RS
| Mouse model . | Human genotype/phenotype . | Onset (mo) . | Penetrance (%) . | Disease entities (as reported) . | Phenotype . | Reference . |
|---|---|---|---|---|---|---|
| MDR | del (13q) | 16-18 | 20-40 | MBL, CLL, DLBCL | Increased B-cell proliferation | 67 |
| MDR/Sf3b1 | del (13q) + Sf3b1-K700E | 18-20 | 25 | CLL | Increased mTOR signaling | 72 |
| Sf3b1/Atm | SF3B1-K700E+del(11q) | 18-22 | 10 | CLL | Increased DNA damage, aberrant 3' splice site selection, low BCR responsiveness | 69 |
| Ikzf3 | IKZF3-L162R | 16-18 | 40 | CLL, DLBCL | Increased follicular and germinal center development, high BCR responsiveness | 70 |
| Rps15 (alone or + Trp53) | RPS15-S138F TP53-mut or del(17p) | 18-20 | 20-30 | CLL | Aberrant MYC signaling | 71 |
| Xpo1 | XPO1-E571K | 6 (SRBC stimulated) | N/A (<100%) | CLL, B cell lymphomas | Aberrant nuclear export | 76 |
| Dnmt3a | Disordered methylation | 10-16 | 60-100 | CLL | Increased B1a-cell survival, aberrant NOTCH signaling | 73-75 |
| CRISPR-multiplexed | LOF in ATM, TP53, CHD2, BIRC3, MGA, SAMHD1, combined with del(13q) | 9-14 | 60-80 | CLL, CLL/RS, RS | Increased DNA damage, MYC signaling | 90 |
| Mouse model . | Human genotype/phenotype . | Onset (mo) . | Penetrance (%) . | Disease entities (as reported) . | Phenotype . | Reference . |
|---|---|---|---|---|---|---|
| MDR | del (13q) | 16-18 | 20-40 | MBL, CLL, DLBCL | Increased B-cell proliferation | 67 |
| MDR/Sf3b1 | del (13q) + Sf3b1-K700E | 18-20 | 25 | CLL | Increased mTOR signaling | 72 |
| Sf3b1/Atm | SF3B1-K700E+del(11q) | 18-22 | 10 | CLL | Increased DNA damage, aberrant 3' splice site selection, low BCR responsiveness | 69 |
| Ikzf3 | IKZF3-L162R | 16-18 | 40 | CLL, DLBCL | Increased follicular and germinal center development, high BCR responsiveness | 70 |
| Rps15 (alone or + Trp53) | RPS15-S138F TP53-mut or del(17p) | 18-20 | 20-30 | CLL | Aberrant MYC signaling | 71 |
| Xpo1 | XPO1-E571K | 6 (SRBC stimulated) | N/A (<100%) | CLL, B cell lymphomas | Aberrant nuclear export | 76 |
| Dnmt3a | Disordered methylation | 10-16 | 60-100 | CLL | Increased B1a-cell survival, aberrant NOTCH signaling | 73-75 |
| CRISPR-multiplexed | LOF in ATM, TP53, CHD2, BIRC3, MGA, SAMHD1, combined with del(13q) | 9-14 | 60-80 | CLL, CLL/RS, RS | Increased DNA damage, MYC signaling | 90 |
N/A, not applicable.