Summary of results for primary human T-ALL cells: no correlation between GSI response and PTEN status
| Sample ID . | NOTCH1 HD mutation . | NOTCH1 PEST mutation . | PTEN mutation . | PTEN protein . | FBW7 mutation . | GSI response . | GSI assay (fresh/NSG) . |
|---|---|---|---|---|---|---|---|
| K550 | L1597H | WT | WT | Positive | WT | Sensitive | NSG |
| KER | WT | WT | WT | Positive | R479Q | Sensitive | Both |
| M18 | WT | P2513L | WT | Positive | WT | Sensitive | NSG |
| M30 | WT | Q2520* | WT | Positive | WT | Sensitive | Both |
| M71 | L1586P | WT | WT | Positive | WT | Sensitive | Fresh |
| M78 | 1612 Del (HG) Ins (QIVVFKRDAHG) | WT | WT | Positive | WT | Sensitive | Fresh |
| D115 | WT | Q2459* | 245 YQFMFLVW* | Negative | WT | Sensitive | NSG |
| M22 | WT | WT | 229 KGTGRQVHVL*/233 PGKTSSCTLSSLSRY LCVVISK* | Negative | WT | Sensitive | NSG |
| M34 | WT | 2469 QGCHPRWSHP* | WT | Negative | WT | Sensitive | Both |
| M53 | WT | Q2417* | WT | Negative | WT | Sensitive | NSG |
| M69 | WT | WT | 233 (R)FSGKTSSCTLSS LSRYLCVVISK* | Negative | WT | Sensitive | Fresh |
| M82 | 1615 Del (QM) Ins (L) | 2515 RVP* | WT | Positive | WT | Resistant | Fresh |
| D135 | WT | 2506 DLLPP* | 233 EEKTSSCTLSSLSR YLCVVISK* | Negative | WT | Resistant | NSG |
| K388 | A1702P | 2402 QSSSSKACSRHHHH HSRTLA* | WT | Positive | WT | ND | |
| K390 | WT | WT | WT | Positive | WT | ND | |
| K419 | Y1717F | WT | WT | Positive | R465C | ND | |
| K424 | WT | WT | WT | Positive | WT | ND | |
| M62 | WT | 2444 RTCSQQTSSSSKACS RHHHHHSRTLA* | WT | Positive | WT | ND | |
| F1313 | L1586P | WT | WT | Positive | WT | ND | |
| U16017 | L1601P | WT | WT | ND | WT | ND |
| Sample ID . | NOTCH1 HD mutation . | NOTCH1 PEST mutation . | PTEN mutation . | PTEN protein . | FBW7 mutation . | GSI response . | GSI assay (fresh/NSG) . |
|---|---|---|---|---|---|---|---|
| K550 | L1597H | WT | WT | Positive | WT | Sensitive | NSG |
| KER | WT | WT | WT | Positive | R479Q | Sensitive | Both |
| M18 | WT | P2513L | WT | Positive | WT | Sensitive | NSG |
| M30 | WT | Q2520* | WT | Positive | WT | Sensitive | Both |
| M71 | L1586P | WT | WT | Positive | WT | Sensitive | Fresh |
| M78 | 1612 Del (HG) Ins (QIVVFKRDAHG) | WT | WT | Positive | WT | Sensitive | Fresh |
| D115 | WT | Q2459* | 245 YQFMFLVW* | Negative | WT | Sensitive | NSG |
| M22 | WT | WT | 229 KGTGRQVHVL*/233 PGKTSSCTLSSLSRY LCVVISK* | Negative | WT | Sensitive | NSG |
| M34 | WT | 2469 QGCHPRWSHP* | WT | Negative | WT | Sensitive | Both |
| M53 | WT | Q2417* | WT | Negative | WT | Sensitive | NSG |
| M69 | WT | WT | 233 (R)FSGKTSSCTLSS LSRYLCVVISK* | Negative | WT | Sensitive | Fresh |
| M82 | 1615 Del (QM) Ins (L) | 2515 RVP* | WT | Positive | WT | Resistant | Fresh |
| D135 | WT | 2506 DLLPP* | 233 EEKTSSCTLSSLSR YLCVVISK* | Negative | WT | Resistant | NSG |
| K388 | A1702P | 2402 QSSSSKACSRHHHH HSRTLA* | WT | Positive | WT | ND | |
| K390 | WT | WT | WT | Positive | WT | ND | |
| K419 | Y1717F | WT | WT | Positive | R465C | ND | |
| K424 | WT | WT | WT | Positive | WT | ND | |
| M62 | WT | 2444 RTCSQQTSSSSKACS RHHHHHSRTLA* | WT | Positive | WT | ND | |
| F1313 | L1586P | WT | WT | Positive | WT | ND | |
| U16017 | L1601P | WT | WT | ND | WT | ND |
NOTCH1, PTEN, and FBW7 status in 20 human T-ALL samples included in this study. GSI response was assessed in 13 of these using lymphoblasts directly from patients (fresh) and/or after expansion as xenografts in NSG mice (NSG). The 3 samples assessed in both situations yielded consistent results. PTEN protein was assessed by intracellular flow cytometry. Observed mutation frequencies among 18 unselected cases are similar to previous reports4,19,20,22 (D115 and D135 were specifically selected for NOTCH1 and PTEN mutation).
WT indicates wild type; and ND, not determined.
Premature stop codon.