Characteristics of the T-ALL patients from the ALL-BFM 2000 study used for the randomized phase 2-like preclinical study
| Parameter . | Patient 1 . | Patient 2 . | Patient 3 . | Patient 4 . | Patient 5 . | Patient 6 . | Patient 7 . | Patient 8 . |
|---|---|---|---|---|---|---|---|---|
| Age at diagnosis, y | 10 | 8 | 16 | 7 | 8 | 13 | 2 | 16 |
| Sex | M | M | M | F | M | M | M | M |
| WBC count (initial), ×109/L | 687 | 303 | 188 | 127 | 166 | 202 | 672 | 76 |
| Blast (PB) initial, % | 80 | 94 | 89 | 94 | 74 | 80.5 | 96.5 | 58 |
| Blast (BM) initial, % | No data | 98 | 88 | 98 | 96 | 84.5 | No data | 92 |
| Immunophenotype | Cortical T | Cortical T | Cortical T | Cortical T | Cortical T | Cortical T | Pre-T | Cortical T |
| Karyotype | 46,XY, t(X;9)(q22;p12), del(6)(q24)[15] | No MP | No MP | 48,XX,+4,+8[15] | 47,XY,-5, del(6)(q23),+9, add(17)(q21), +mar[11] | 46,XY, t(1;14)(p32∼33;q11) [15] | 46,XY, t(1;6)(p34;q22), del(9)(p21)[12]/46,XY[3] | 46,XY, del(4)(q31), add(7)(q34), add(15)(q13), inc[3]/46,XY[12] |
| Transcription factors (quantitative PCR*) | TAL1, LMO2, LYL | LMO1 | LMO2, LYL, MYB | HOXA9, HOXA10, LMO2, LYL, MYB | TAL1, LMO2, LYL | TAL1, LMO2 | LMO2, LYL | TAL1 |
| Mutations† | None detected | Notch HD-N1 | Notch PEST 1 | PTEN Ex 7 | WT1 Ex7 | Notch PEST 1 | Stat5B Ex16 | Fbxw7 Ex 9+10 |
| WT1 Ex7 | Fbxw7 Ex 9+10 | Notch HD-N1 | ||||||
| Prednisone response | Poor | Poor | Good | Good | Good | Good | Poor | Good |
| Final risk group | HR | HR | MR | MR | MR | SR | HR | SR |
| Blasts (BM) d15, % | 36 | 1 | Not done | 73 | 66 | 16 | 83 | 0 |
| MRD day 33 | 1E-2 | 1E-3 | 1E-3 | ND | 1E-2 | 1E-8 | 1E-1 | 1E-8 |
| MRD day 78 | 1E-1 | 1E-4 | 1E-4 | ND | 1E-4 | 1E-8 | 1E-4 | 1E-8 |
| Relapse | No | No | No | No | No | No | Yes | No |
| Death | No | Yes | No | Yes | No | No | Yes | No |
| Cause of death | N/A | Infection during chemotherapy | N/A | Infection during chemotherapy | N/A | N/A | Toxicity in relapse therapy | N/A |
| CD38 MFI‡ | 7.99 | 31.86 | 19.62 | 23.01 | 50.75 | 9.38 | 28.15 | 28.71 |
| CD38 mRNA‡ | 4.77 | 8.02 | 2.77 | 4.96 | 28.87 | 1.55 | 1.49 | 1.2 |
| Increased survival with DARA | Yes | Yes | Yes | Yes | Yes | No | No | No |
| Increased survival with chemo+DARA | No | Yes | Yes | Yes | Yes | No | No | No |
| Parameter . | Patient 1 . | Patient 2 . | Patient 3 . | Patient 4 . | Patient 5 . | Patient 6 . | Patient 7 . | Patient 8 . |
|---|---|---|---|---|---|---|---|---|
| Age at diagnosis, y | 10 | 8 | 16 | 7 | 8 | 13 | 2 | 16 |
| Sex | M | M | M | F | M | M | M | M |
| WBC count (initial), ×109/L | 687 | 303 | 188 | 127 | 166 | 202 | 672 | 76 |
| Blast (PB) initial, % | 80 | 94 | 89 | 94 | 74 | 80.5 | 96.5 | 58 |
| Blast (BM) initial, % | No data | 98 | 88 | 98 | 96 | 84.5 | No data | 92 |
| Immunophenotype | Cortical T | Cortical T | Cortical T | Cortical T | Cortical T | Cortical T | Pre-T | Cortical T |
| Karyotype | 46,XY, t(X;9)(q22;p12), del(6)(q24)[15] | No MP | No MP | 48,XX,+4,+8[15] | 47,XY,-5, del(6)(q23),+9, add(17)(q21), +mar[11] | 46,XY, t(1;14)(p32∼33;q11) [15] | 46,XY, t(1;6)(p34;q22), del(9)(p21)[12]/46,XY[3] | 46,XY, del(4)(q31), add(7)(q34), add(15)(q13), inc[3]/46,XY[12] |
| Transcription factors (quantitative PCR*) | TAL1, LMO2, LYL | LMO1 | LMO2, LYL, MYB | HOXA9, HOXA10, LMO2, LYL, MYB | TAL1, LMO2, LYL | TAL1, LMO2 | LMO2, LYL | TAL1 |
| Mutations† | None detected | Notch HD-N1 | Notch PEST 1 | PTEN Ex 7 | WT1 Ex7 | Notch PEST 1 | Stat5B Ex16 | Fbxw7 Ex 9+10 |
| WT1 Ex7 | Fbxw7 Ex 9+10 | Notch HD-N1 | ||||||
| Prednisone response | Poor | Poor | Good | Good | Good | Good | Poor | Good |
| Final risk group | HR | HR | MR | MR | MR | SR | HR | SR |
| Blasts (BM) d15, % | 36 | 1 | Not done | 73 | 66 | 16 | 83 | 0 |
| MRD day 33 | 1E-2 | 1E-3 | 1E-3 | ND | 1E-2 | 1E-8 | 1E-1 | 1E-8 |
| MRD day 78 | 1E-1 | 1E-4 | 1E-4 | ND | 1E-4 | 1E-8 | 1E-4 | 1E-8 |
| Relapse | No | No | No | No | No | No | Yes | No |
| Death | No | Yes | No | Yes | No | No | Yes | No |
| Cause of death | N/A | Infection during chemotherapy | N/A | Infection during chemotherapy | N/A | N/A | Toxicity in relapse therapy | N/A |
| CD38 MFI‡ | 7.99 | 31.86 | 19.62 | 23.01 | 50.75 | 9.38 | 28.15 | 28.71 |
| CD38 mRNA‡ | 4.77 | 8.02 | 2.77 | 4.96 | 28.87 | 1.55 | 1.49 | 1.2 |
| Increased survival with DARA | Yes | Yes | Yes | Yes | Yes | No | No | No |
| Increased survival with chemo+DARA | No | Yes | Yes | Yes | Yes | No | No | No |
BM, bone marrow; F, female; Fbxw7, F-box and WD repeat domain containing 7; HOXA9/10, homeobox A9/10; HR, high risk; IL7R, interleukin-7 receptor; JAK1, janus kinase 2; LEF, lymphoid enhancer binding factor; LMO1/2, LIM domain only 1/2; LYL1, LYL1 basic helix-loop-helix family member; M, male; MEF2C, myocyte enhancer factor 2C; MR, medium risk; MRD, minimal residual disease; MYB, MYB proto-oncogene, transcription factor; N/A, not applicable; ND, not determined; no MP, no metaphases to analyze; Notch-HD N1, Notch N terminal heterodimerization domain; Notch PEST1, Notch proline, glutamic acid, serine, threonine–rich domain; PB, peripheral blood; PTEN, phosphatase and tensin homolog; SR, standard risk; STAT5B, signal transducer and activator of transcription 5B; TAL1, T-cell acute lymphocytic leukemia 1; TLX1/3, T-cell leukemia homeobox 1/3; WBC, white blood cell; WT1, WT1 transcription factor.
Relative expression values >10-fold beyond control (normal human T cells); see also supplemental Figure 3 and supplemental Methods. TLX1 and TLX3 were below the cutoff in all samples but borderline in patients 2 and 4. MEF2C was also tested, but all patients were negative.
Mutations in IL7R exon 6; JAK1 exons 15, 16, and 18; and LEF exons 2 and 3 were also tested but not detected.
Normalized to MFI/mRNA values in RPMI8226 multiple myeloma cells, respectively.