Clinical characteristics of BCP-ALL and T-ALL PDX samples used in BCP-ALL/T-ALL phase 2-like overt leukemia study (refers toFigure 3 )
| Patient characteristics . | PDX data . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PDX no. . | Age at diagnosis, y . | Sex . | White blood cell count/µl . | Relapse . | Death . | Immunophenotype . | Cytogenetics∗ . | Relevant mutations† . | Sample origin . | CD127+ cells,‡ % . | Delta PBB§ . | Survival control‖ . | Survival LUSV¶ . |
| BCP-ALL 1 | 10.4 | M | 7.8 | No | No | Common B-ALL | TCF3::PBX1 | n. d. | De novo BCP-ALL | 65 | 68.42 | 84 | 129 |
| BCP-ALL 2 | 14.8 | M | 26.8 | No | No | Pre-B-ALL | TCF3::PBX1 | n. d. | De novo BCP-ALL | 83.4 | 63.25 | 99 | 227 |
| BCP-ALL 3 | 8.6 | F | 12.6 | No | No | Common B-ALL | TCF3::PBX1 | NRAS (p.G13D) | De novo BCP-ALL | 45.9 | 25.9 | 59 | 60 |
| BCP-ALL 4∗∗ | 13.4 | M | 12.32 | Yes | Yes | Pre-B-ALL | TCF3::PBX1 | n. d. | De novo BCP-ALL | 67.7 | 52.79 | 56 | 85 |
| BCP-ALL 5∗∗ | 13.4 | M | 12.32 | Yes | Yes | Pre–B-ALL | TCF3::PBX1 | n. d. | R/R BCP-ALL | 77.7 | 74.4 | 65 | 111 |
| BCP-ALL 6 | 17.3 | F | 13.3 | Yes | No | Common B-ALL | BCR::ABL1 | n. d. | De novo BCP-ALL | 65.5 | 68.4 | 58 | 135 |
| BCP-ALL 7 | 9.8 | F | 132 | No | No | Common B-ALL | BCR::ABL1 | n. d. | De novo BCP-ALL | 38.2 | 46 | 61 | 62 |
| BCP-ALL 8 | 9 | M | 3.5 | No | No | Common B-ALL | BCR::ABL1 | n. d. | De novo BCP-ALL | 59.4 | 51.6 | 84 | 119 |
| BCP-ALL 9 | 0.7 | F | 103 | No | No | Pre–B-ALL | KMT2A::MLLT1 | n. d. | De novo BCP-ALL | 45.1 | 24.9 | 55 | 62 |
| BCP-ALL 10 | 1.2 | M | 60.8 | Yes | Yes | Common B-ALL | KMT2A::MLLT10 | n. d. | De novo BCP-ALL | 29.8 | 30.9 | 37 | 44 |
| BCP-ALL 11 | 1.6 | M | 288.4 | No | No | B-ALL | B-other# (EBF1::PDGFRB) | n. d. | De novo BCP-ALL | 37.5 | 2 | 88 | 97 |
| BCP-ALL 12 | 3.1 | F | 103.53 | Yes | No | Common B-ALL | B-other (DNMT3B::PAX5) | IL7R (p.L243_T244delinsRCGI) (GoF) | De novo BCP-ALL | 56.6 | 73.18 | 83 | 228 |
| BCP-ALL 13 | 10.7 | M | 113 | No | No | Common B-ALL | TCF3::PBX1 | n. d. | De novo BCP-ALL | 86.8 | 56.11 | 77 | 100 |
| BCP-ALL 14 | 5 | M | 204 | Yes | Yes | Common B-ALL | B-other (BCR::JAK2) | n. d. | De novo BCP-ALL | 79.3 | 35.5 | 49 | 74 |
| BCP-ALL 15 | 7 | F | 115 | No | No | Pre–B-ALL | B-other (P2RY8::CRLF2) | JAK2 (p.R683G) | De novo BCP-ALL | 99.5 | 81.5 | 76 | 200∗∗ |
| T-ALL 1 | 2 | M | 672 | Yes | Yes | Pre–T-ALL | — | STAT5B (p.N642H) | De novo T-ALL | 62.6 | 78.62 | 38 | 71 |
| T-ALL 2 | 7 | M | 872 | No | No | Cortical T-ALL | — | NOTCH1 (p.V1676D) / NRAS (p.Y64N) | De novo T-ALL | 59.80 | 88.83 | 136 | 211 |
| T-ALL 6 | 4 | M | 15.8 | Yes | Yes | Mature T-ALL | — | n. d. | R/R T-ALL | 62.90 | 39.86 | 57 | 80 |
| T-ALL 9 | 27 | F | 3.4 | Yes | Yes | ETP-ALL | — | NRAS (p.G12C) PTEN (p.R142Q) NOTCH1 (p.L1574P) | De novo T-ALL (adult) | 32.10 | 32.60 | 122 | 147 |
| T-ALL 10 | 4 | M | 10.23 | Yes | Yes | Pre–T-ALL | — | n. d. | R/R T-ALL | 36.90 | 20.52 | 50 | 71 |
| T-ALL 11 | 8 | F | 170.9 | Yes | Yes | Cortical T-ALL | — | NOTCH1 (p.L1600P) | R/R T-ALL | 77.3 | 35.22 | 37 | 57 |
| T-ALL 12 | 2 | F | 550 | Yes | No | Cortical T-ALL | — | n. d. | R/R T-ALL | 20.40 | 24.20 | 38 | 80 |
| T-ALL 13 | 11 | M | 226.5 | Yes | Yes | Mature T-ALL | — | n. d. | R/R T-ALL | 63.20 | 48.10 | 39 | 49 |
| T-ALL 14 | 9 | M | 36.3 | Yes | No | Cortical T-ALL | — | n. d. | R/R T-ALL | 26.60 | 18.05 | 38 | 60 |
| Patient characteristics . | PDX data . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PDX no. . | Age at diagnosis, y . | Sex . | White blood cell count/µl . | Relapse . | Death . | Immunophenotype . | Cytogenetics∗ . | Relevant mutations† . | Sample origin . | CD127+ cells,‡ % . | Delta PBB§ . | Survival control‖ . | Survival LUSV¶ . |
| BCP-ALL 1 | 10.4 | M | 7.8 | No | No | Common B-ALL | TCF3::PBX1 | n. d. | De novo BCP-ALL | 65 | 68.42 | 84 | 129 |
| BCP-ALL 2 | 14.8 | M | 26.8 | No | No | Pre-B-ALL | TCF3::PBX1 | n. d. | De novo BCP-ALL | 83.4 | 63.25 | 99 | 227 |
| BCP-ALL 3 | 8.6 | F | 12.6 | No | No | Common B-ALL | TCF3::PBX1 | NRAS (p.G13D) | De novo BCP-ALL | 45.9 | 25.9 | 59 | 60 |
| BCP-ALL 4∗∗ | 13.4 | M | 12.32 | Yes | Yes | Pre-B-ALL | TCF3::PBX1 | n. d. | De novo BCP-ALL | 67.7 | 52.79 | 56 | 85 |
| BCP-ALL 5∗∗ | 13.4 | M | 12.32 | Yes | Yes | Pre–B-ALL | TCF3::PBX1 | n. d. | R/R BCP-ALL | 77.7 | 74.4 | 65 | 111 |
| BCP-ALL 6 | 17.3 | F | 13.3 | Yes | No | Common B-ALL | BCR::ABL1 | n. d. | De novo BCP-ALL | 65.5 | 68.4 | 58 | 135 |
| BCP-ALL 7 | 9.8 | F | 132 | No | No | Common B-ALL | BCR::ABL1 | n. d. | De novo BCP-ALL | 38.2 | 46 | 61 | 62 |
| BCP-ALL 8 | 9 | M | 3.5 | No | No | Common B-ALL | BCR::ABL1 | n. d. | De novo BCP-ALL | 59.4 | 51.6 | 84 | 119 |
| BCP-ALL 9 | 0.7 | F | 103 | No | No | Pre–B-ALL | KMT2A::MLLT1 | n. d. | De novo BCP-ALL | 45.1 | 24.9 | 55 | 62 |
| BCP-ALL 10 | 1.2 | M | 60.8 | Yes | Yes | Common B-ALL | KMT2A::MLLT10 | n. d. | De novo BCP-ALL | 29.8 | 30.9 | 37 | 44 |
| BCP-ALL 11 | 1.6 | M | 288.4 | No | No | B-ALL | B-other# (EBF1::PDGFRB) | n. d. | De novo BCP-ALL | 37.5 | 2 | 88 | 97 |
| BCP-ALL 12 | 3.1 | F | 103.53 | Yes | No | Common B-ALL | B-other (DNMT3B::PAX5) | IL7R (p.L243_T244delinsRCGI) (GoF) | De novo BCP-ALL | 56.6 | 73.18 | 83 | 228 |
| BCP-ALL 13 | 10.7 | M | 113 | No | No | Common B-ALL | TCF3::PBX1 | n. d. | De novo BCP-ALL | 86.8 | 56.11 | 77 | 100 |
| BCP-ALL 14 | 5 | M | 204 | Yes | Yes | Common B-ALL | B-other (BCR::JAK2) | n. d. | De novo BCP-ALL | 79.3 | 35.5 | 49 | 74 |
| BCP-ALL 15 | 7 | F | 115 | No | No | Pre–B-ALL | B-other (P2RY8::CRLF2) | JAK2 (p.R683G) | De novo BCP-ALL | 99.5 | 81.5 | 76 | 200∗∗ |
| T-ALL 1 | 2 | M | 672 | Yes | Yes | Pre–T-ALL | — | STAT5B (p.N642H) | De novo T-ALL | 62.6 | 78.62 | 38 | 71 |
| T-ALL 2 | 7 | M | 872 | No | No | Cortical T-ALL | — | NOTCH1 (p.V1676D) / NRAS (p.Y64N) | De novo T-ALL | 59.80 | 88.83 | 136 | 211 |
| T-ALL 6 | 4 | M | 15.8 | Yes | Yes | Mature T-ALL | — | n. d. | R/R T-ALL | 62.90 | 39.86 | 57 | 80 |
| T-ALL 9 | 27 | F | 3.4 | Yes | Yes | ETP-ALL | — | NRAS (p.G12C) PTEN (p.R142Q) NOTCH1 (p.L1574P) | De novo T-ALL (adult) | 32.10 | 32.60 | 122 | 147 |
| T-ALL 10 | 4 | M | 10.23 | Yes | Yes | Pre–T-ALL | — | n. d. | R/R T-ALL | 36.90 | 20.52 | 50 | 71 |
| T-ALL 11 | 8 | F | 170.9 | Yes | Yes | Cortical T-ALL | — | NOTCH1 (p.L1600P) | R/R T-ALL | 77.3 | 35.22 | 37 | 57 |
| T-ALL 12 | 2 | F | 550 | Yes | No | Cortical T-ALL | — | n. d. | R/R T-ALL | 20.40 | 24.20 | 38 | 80 |
| T-ALL 13 | 11 | M | 226.5 | Yes | Yes | Mature T-ALL | — | n. d. | R/R T-ALL | 63.20 | 48.10 | 39 | 49 |
| T-ALL 14 | 9 | M | 36.3 | Yes | No | Cortical T-ALL | — | n. d. | R/R T-ALL | 26.60 | 18.05 | 38 | 60 |
ETP, Early T-cell precursor; F, female; M, male; n. d., none detected.
Stratification relevant lesions were diagnosed by fluorescence in situ hybridization or targeted RNA sequencing as described previously.31
Mutations were detected via targeted DNA sequencing using a custom DNA hybridization panel covering 151 genes frequently mutated in hematologic malignancies as described previously.31
CD127+ cells of all cells in the ALL cell population.
Reduction of peripheral blood blasts (PBB) of LUSV-treated mice compared with control-treated mice by the time one of the corresponding PDX animals or animal groups showed signs of overt leukemia (ΔPBB = PBBControl-treated – PBBLUSV-treated).
Survival of control–treated PDX mouse.
Survival of LUSV–treated PDX mouse.
B-other: BCP-ALL cases without the stratification relevant translocations ETV6::RUNX1, BCR::ABL1, TCF3::PBX1, KMT2A-rearrangements.
Matched pair obtained from initial diagnosis and relapse.