Molecular characteristics of the T-ALL patients used for the randomized phase 2–like preclinical study
| Patient . | Age at diagnosis (y) . | Sex . | WBC count (initial)/µL . | Blast (PB) initial (%) . | Blast (BM) initial (%) . | Immuno phenotype . | Karyotype . | Transcription factors (qPCR)* . | Mutations . | Treatment protocol† . | Pred response . | Final risk group‡ . | Blasts (BM) day 15 (%) . | MRD day +33 . | MRD day +78 . | Relapse . | Death . | Cause of death . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient 1 | 8 | M | 303 | 94 | 98 | Cortical T | No MP | LMO1 | Notch HD-N1; WT1 Ex7 | 2000 | Poor | HR | 1 | 1.00E-3 | 1.00E-4 | No | Yes | Infection during chemo therapy |
| Patient 2 | 8 | M | 166 | 74 | 96 | Cortical T | 47,XY,-5, del(6)(q23),+9, add(17)(q21) | TAL1, LMO2, LYL1 | WT1 Ex7 | 2000 | Good | MR | 66 | 1.00E-2 | 1.00E-4 | No | No | |
| Patient 3 | 7 | F | 127 | 94 | 98 | Cortical T | 48,XX+4,+8[15] | HOXA9, HOXA10, LMO2, LYL1, MYB | Fbxw7 Ex9 + 10 | 2000 | Good | MR | 73 | n.o. | n.o. | No | Yes | Infection during chemo therapy |
| Patient 4 | 12 | M | 11 720 | 79 | 83.5 | Cortical T | No MP | TAL1, LYL1, MYB | None | 2000 | Good | HR | 2 | 1.00E-2 | 1.00E-2 | Yes | No | |
| Patient 5 | 2 | F | 105000 | 84 | 95 | Cortical T | 46,XX t(11;14)(p13;q11), mar,inc[cp3] /46, XX,inc[27] FISH: Transl. In Chr.14 | LYL1 | None | 2009 | Good | MR | 1 | 1.00E-3 | 1.00E-8 | Yes | Yes | Third relapse |
| Patient 6 | 2 | M | 672 | 96.5 | n.o. | Pre-T | 46,XY,t(1;6)(p34;q22), del(9)(p21)[12]/46,XY[3] | LMO2, LYL1 | Stat5B Ex16 | 2000 | Poor | HR | 83 | 1.00E-1 | 1.00E-4 | Yes | Yes | Toxicity in relapse therapy |
| Patient 7 | 16 | M | 188 | 89 | 88 | Cortical T | No MP | LMO2, LYL1, MYB | Notch PEST 1 | 2000 | Good | MR | n.o. | 1.00E-3 | 1.00E-4 | No | No | |
| Patient 8 | 10 | M | 687 | 80 | n.o. | Cortical T | 46,XY, t(X;9)(q22;p12), del(6)(q24)[15] | TAL1, LMO2, LYL1 | None | 2000 | Poor | HR | 36 | 1.00E-2 | 1.00E-1 | No | No | |
| Patient 9 | 6 | M | 56 000 | 63 | 92 | Cortical T | 46,XY, inv(9)(p13;q13) | TLX1, TAL1, HOXA9, HOXA10, LMO1, LYL1, MYB | Fbxw7; Notch1 HD | 2000 | Poor | HR | 6.5 | 1.00E-3 | Negative | No | Yes | GvHD post-SCT |
| Patient 10 | 15 | M | 166 000 | 81.5 | n.o. | Cortical T | No MP | TAL1, HOXA9, HOXA10, LMO2, LYL1, MYB | PTEN Ex 7; Stat5B | 2000 | Good | MR | 27 | 1.00E-2 | 1.00E-4 | No | No | |
| Patient 11 | 16 | M | 76 | 58 | 92 | Cortical T | 46,XY,del(4)(q31), add(7)(q34), add(15)(q13), inc[3]/46,XY[12] | TAL1 | Fbxw7 Ex 9 + 10; Notch HD-N1 | 2000 | Good | SR | 0 | 1.00E-8 | 1.00E-8 | No | No | |
| Patient 12 | 13 | F | 107 000 | 79 | 71 | Pre-T | 46,XX, der(9)t(3;9)(q26;p21), del(9)(q22q32), add(16)(q12)[10] | TAL1, LYL1 | Fbxw7 Ex 9 | 2000 | Poor | HR | 24.5 | 1.00E-1 | 1.00E-2 | Yes | Yes | Progressive disease |
| Patient . | Age at diagnosis (y) . | Sex . | WBC count (initial)/µL . | Blast (PB) initial (%) . | Blast (BM) initial (%) . | Immuno phenotype . | Karyotype . | Transcription factors (qPCR)* . | Mutations . | Treatment protocol† . | Pred response . | Final risk group‡ . | Blasts (BM) day 15 (%) . | MRD day +33 . | MRD day +78 . | Relapse . | Death . | Cause of death . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient 1 | 8 | M | 303 | 94 | 98 | Cortical T | No MP | LMO1 | Notch HD-N1; WT1 Ex7 | 2000 | Poor | HR | 1 | 1.00E-3 | 1.00E-4 | No | Yes | Infection during chemo therapy |
| Patient 2 | 8 | M | 166 | 74 | 96 | Cortical T | 47,XY,-5, del(6)(q23),+9, add(17)(q21) | TAL1, LMO2, LYL1 | WT1 Ex7 | 2000 | Good | MR | 66 | 1.00E-2 | 1.00E-4 | No | No | |
| Patient 3 | 7 | F | 127 | 94 | 98 | Cortical T | 48,XX+4,+8[15] | HOXA9, HOXA10, LMO2, LYL1, MYB | Fbxw7 Ex9 + 10 | 2000 | Good | MR | 73 | n.o. | n.o. | No | Yes | Infection during chemo therapy |
| Patient 4 | 12 | M | 11 720 | 79 | 83.5 | Cortical T | No MP | TAL1, LYL1, MYB | None | 2000 | Good | HR | 2 | 1.00E-2 | 1.00E-2 | Yes | No | |
| Patient 5 | 2 | F | 105000 | 84 | 95 | Cortical T | 46,XX t(11;14)(p13;q11), mar,inc[cp3] /46, XX,inc[27] FISH: Transl. In Chr.14 | LYL1 | None | 2009 | Good | MR | 1 | 1.00E-3 | 1.00E-8 | Yes | Yes | Third relapse |
| Patient 6 | 2 | M | 672 | 96.5 | n.o. | Pre-T | 46,XY,t(1;6)(p34;q22), del(9)(p21)[12]/46,XY[3] | LMO2, LYL1 | Stat5B Ex16 | 2000 | Poor | HR | 83 | 1.00E-1 | 1.00E-4 | Yes | Yes | Toxicity in relapse therapy |
| Patient 7 | 16 | M | 188 | 89 | 88 | Cortical T | No MP | LMO2, LYL1, MYB | Notch PEST 1 | 2000 | Good | MR | n.o. | 1.00E-3 | 1.00E-4 | No | No | |
| Patient 8 | 10 | M | 687 | 80 | n.o. | Cortical T | 46,XY, t(X;9)(q22;p12), del(6)(q24)[15] | TAL1, LMO2, LYL1 | None | 2000 | Poor | HR | 36 | 1.00E-2 | 1.00E-1 | No | No | |
| Patient 9 | 6 | M | 56 000 | 63 | 92 | Cortical T | 46,XY, inv(9)(p13;q13) | TLX1, TAL1, HOXA9, HOXA10, LMO1, LYL1, MYB | Fbxw7; Notch1 HD | 2000 | Poor | HR | 6.5 | 1.00E-3 | Negative | No | Yes | GvHD post-SCT |
| Patient 10 | 15 | M | 166 000 | 81.5 | n.o. | Cortical T | No MP | TAL1, HOXA9, HOXA10, LMO2, LYL1, MYB | PTEN Ex 7; Stat5B | 2000 | Good | MR | 27 | 1.00E-2 | 1.00E-4 | No | No | |
| Patient 11 | 16 | M | 76 | 58 | 92 | Cortical T | 46,XY,del(4)(q31), add(7)(q34), add(15)(q13), inc[3]/46,XY[12] | TAL1 | Fbxw7 Ex 9 + 10; Notch HD-N1 | 2000 | Good | SR | 0 | 1.00E-8 | 1.00E-8 | No | No | |
| Patient 12 | 13 | F | 107 000 | 79 | 71 | Pre-T | 46,XX, der(9)t(3;9)(q26;p21), del(9)(q22q32), add(16)(q12)[10] | TAL1, LYL1 | Fbxw7 Ex 9 | 2000 | Poor | HR | 24.5 | 1.00E-1 | 1.00E-2 | Yes | Yes | Progressive disease |
BM, bone marrow; Ex, Exon; F, female; Fbxw7, F-box and WD repeat domain containing 7; GvHD, graft-versus-host-disease; HOXA9/10, homeobox A9/10; HR, high risk; LMO1/2, LIM domain only 1/2; LYL1, LYL1 basic helix-loop helix family member; M, male; MP, meta-phase; MR, medium risk; MRD, Minimal Residual Disease; MYB, MYB proto-oncogene; n.o., not obtainable; Notch HD-N1, Notch N-terminal heterodimerization domain; Notch PEST 1, Notch proline, glutamic acid, serine, threonine–rich domain; Notch1 HD, Notch 1 heterodimerization domain; PB, peripheral blood; Pred, prednisone; PTEN, phosphatase and tensin homolog; qPCR, quantitative real-time polymerase chain reaction; SCT, stem cell transplant; SR, standard risk; Stat5B, signal transducer and activator of transcription 5B; TAL1, T-cell ALL 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); TLX3 was below cutoff in all samples.
Treatment protocol: AIEOP-BFM ALL.
Stratification according to AIEOP-BFM ALL 2000/2009 treatment protocol. Detailed information regarding stratification is provided in the supplemental Methods.