Cytogenetic profile of childhood ALL with and without CRLF2 deregulation
| Chromosomal abnormality . | Tested, n (%) . | CRLF2 deregulation . | |||||
|---|---|---|---|---|---|---|---|
| Total cohort . | Non-DS cohort . | DS cohort . | |||||
| Yes, n (%) . | No, n (%) . | Yes, n (%) . | No, n (%) . | Yes, n (%) . | No, n (%) . | ||
| All patients | 865 (100) | 52 (100) | 813 (100) | 38 (100) | 801 (100) | 14 (100) | 12 (100) |
| Primary abnormalities | |||||||
| High hyperdiploidy | 294 (37) | 6 (12) | 288 (35) | 6 (16) | 288 (36) | 0 (0) | 0 (0) |
| ETV6-RUNX1 | 220 (26) | 0 (0) | 220 (27) | 0 (0) | 215 (27) | 0 (0) | 5 (42) |
| t(1;19)(q23;p13) | 26 (4) | 0 (0) | 26 (3) | 0 (0) | 26 (3) | 0 (0) | 0 (0) |
| t(9;22)(q34;q11.2) | 23 (3) | 0 (0) | 23 (3) | 0 (0) | 23 (3) | 0 (0) | 0 (0) |
| iAMP21 | 20 (2) | 5 (10) | 15 (2) | 5 (13) | 15 (2) | 0 (0) | 0 (0) |
| MLL translocations | 16 (2) | 0 (0) | 16 (2) | 0 (0) | 16 (2) | 0 (0) | 0 (0) |
| Near haploidy | 7 (< 1) | 1 (2) | 6 (< 1) | 1 (3) | 6 (< 1) | 0 (0) | 0 (0) |
| Low hypodiploidy | 2 (< 1) | 0 (0) | 2 (< 1) | 0 (0) | 2 (< 1) | 0 (0) | 0 (0) |
| IGH@-CEBP | 6 (7)† | 0 (0) | 6 (< 1) | 0 (0) | 5 (< 1) | 0 (0) | 1 (8) |
| IGH@-ID4 | 3 (3)† | 0 (0) | 3 (< 1) | 0 (0) | 3 (< 1) | 0 (0) | 0 (0) |
| Secondary abnormalities | |||||||
| del(6q) | 41 (5) | 2 (4) | 39 (5) | 1 (3) | 38 (5) | 1 (7) | 1 (8) |
| abnormal 9p | 95 (13) | 7 (13) | 88 (11) | 4 (11) | 87 (11) | 3 (21) | 1 (8) |
| abnormal 11q | 38 (5) | 1 (2) | 37 (5) | 0 (0) | 36 (5) | 1 (7) | 1 (8) |
| abnormal 17p | 32 (4) | 2 (4) | 30 (4) | 2 (5) | 30 (4) | 0 (0) | 0 (0) |
| Loss of 13q | 25 (3) | 0 (0) | 25 (3) | 0 (0) | 25 (3) | 0 (0) | 0 (0) |
| dup(1q) | 21 (3) | 1 (2) | 20 (3) | 1 (3) | 20 (2) | 0 (0) | 0 (0) |
| −7 | 10 (1) | 0 (0) | 10 (1) | 0 (0) | 9 (1) | 0 (0) | 1 (8) |
| dic(9;20)(p13;q11) | 8 (1) | 1 (2) | 7 (< 1) | 1 (3) | 7 (< 1) | 0 (0) | 0 (0) |
| dic(9;12)(p11∼21;p11∼13) | 8 (1) | 0 (0) | 8 (< 1) | 0 (0) | 8 (1) | 0 (0) | 0 (0) |
| Microdeletions and mutations* | |||||||
| IKZF1 deletions‡ | 19/49 (39) | 15/37 (41) | 4/12 (33) | ||||
| CDKN2A/B deletions | 16/43 (37) | 14/33 (42) | 2/10 (20) | ||||
| PAX5 deletions | 18/43 (42) | 14/33 (42) | 4/10 (40) | ||||
| EBF1 deletions | 4/43 (9) | 4/33 (12) | 0/10 (0) | ||||
| ETV6 deletions | 3/43 (7) | 2/33 (6) | 1/10 (10) | ||||
| BTG1 deletions | 2/43 (5) | 1/33 (3) | 1/10 (10) | ||||
| RB1 deletions | 1/43 (2) | 1/33 (3) | 0/10 (0) | ||||
| JAK2 mutations§ | 10/20 (50) | 4/11 (36) | 6/9 (67) | ||||
| Cytogenetic risk group‖ | |||||||
| Good risk | 510 (62) | 6 (13) | 504 (65) | 6 (18) | 499 (65) | 0 (0) | 5 (46) |
| Intermediate risk | 216 (26) | 33 (72) | 183 (24) | 21 (62) | 177 (23) | 12 (100) | 6 (55) |
| Poor risk | 95 (12) | 7 (15) | 88 (11) | 7 (21) | 88 (12) | 0 (0) | 0 (0) |
| Unknown/not classified | 44 | 6 | 38 | 4 | 37 | 2 | 1 |
| Chromosomal abnormality . | Tested, n (%) . | CRLF2 deregulation . | |||||
|---|---|---|---|---|---|---|---|
| Total cohort . | Non-DS cohort . | DS cohort . | |||||
| Yes, n (%) . | No, n (%) . | Yes, n (%) . | No, n (%) . | Yes, n (%) . | No, n (%) . | ||
| All patients | 865 (100) | 52 (100) | 813 (100) | 38 (100) | 801 (100) | 14 (100) | 12 (100) |
| Primary abnormalities | |||||||
| High hyperdiploidy | 294 (37) | 6 (12) | 288 (35) | 6 (16) | 288 (36) | 0 (0) | 0 (0) |
| ETV6-RUNX1 | 220 (26) | 0 (0) | 220 (27) | 0 (0) | 215 (27) | 0 (0) | 5 (42) |
| t(1;19)(q23;p13) | 26 (4) | 0 (0) | 26 (3) | 0 (0) | 26 (3) | 0 (0) | 0 (0) |
| t(9;22)(q34;q11.2) | 23 (3) | 0 (0) | 23 (3) | 0 (0) | 23 (3) | 0 (0) | 0 (0) |
| iAMP21 | 20 (2) | 5 (10) | 15 (2) | 5 (13) | 15 (2) | 0 (0) | 0 (0) |
| MLL translocations | 16 (2) | 0 (0) | 16 (2) | 0 (0) | 16 (2) | 0 (0) | 0 (0) |
| Near haploidy | 7 (< 1) | 1 (2) | 6 (< 1) | 1 (3) | 6 (< 1) | 0 (0) | 0 (0) |
| Low hypodiploidy | 2 (< 1) | 0 (0) | 2 (< 1) | 0 (0) | 2 (< 1) | 0 (0) | 0 (0) |
| IGH@-CEBP | 6 (7)† | 0 (0) | 6 (< 1) | 0 (0) | 5 (< 1) | 0 (0) | 1 (8) |
| IGH@-ID4 | 3 (3)† | 0 (0) | 3 (< 1) | 0 (0) | 3 (< 1) | 0 (0) | 0 (0) |
| Secondary abnormalities | |||||||
| del(6q) | 41 (5) | 2 (4) | 39 (5) | 1 (3) | 38 (5) | 1 (7) | 1 (8) |
| abnormal 9p | 95 (13) | 7 (13) | 88 (11) | 4 (11) | 87 (11) | 3 (21) | 1 (8) |
| abnormal 11q | 38 (5) | 1 (2) | 37 (5) | 0 (0) | 36 (5) | 1 (7) | 1 (8) |
| abnormal 17p | 32 (4) | 2 (4) | 30 (4) | 2 (5) | 30 (4) | 0 (0) | 0 (0) |
| Loss of 13q | 25 (3) | 0 (0) | 25 (3) | 0 (0) | 25 (3) | 0 (0) | 0 (0) |
| dup(1q) | 21 (3) | 1 (2) | 20 (3) | 1 (3) | 20 (2) | 0 (0) | 0 (0) |
| −7 | 10 (1) | 0 (0) | 10 (1) | 0 (0) | 9 (1) | 0 (0) | 1 (8) |
| dic(9;20)(p13;q11) | 8 (1) | 1 (2) | 7 (< 1) | 1 (3) | 7 (< 1) | 0 (0) | 0 (0) |
| dic(9;12)(p11∼21;p11∼13) | 8 (1) | 0 (0) | 8 (< 1) | 0 (0) | 8 (1) | 0 (0) | 0 (0) |
| Microdeletions and mutations* | |||||||
| IKZF1 deletions‡ | 19/49 (39) | 15/37 (41) | 4/12 (33) | ||||
| CDKN2A/B deletions | 16/43 (37) | 14/33 (42) | 2/10 (20) | ||||
| PAX5 deletions | 18/43 (42) | 14/33 (42) | 4/10 (40) | ||||
| EBF1 deletions | 4/43 (9) | 4/33 (12) | 0/10 (0) | ||||
| ETV6 deletions | 3/43 (7) | 2/33 (6) | 1/10 (10) | ||||
| BTG1 deletions | 2/43 (5) | 1/33 (3) | 1/10 (10) | ||||
| RB1 deletions | 1/43 (2) | 1/33 (3) | 0/10 (0) | ||||
| JAK2 mutations§ | 10/20 (50) | 4/11 (36) | 6/9 (67) | ||||
| Cytogenetic risk group‖ | |||||||
| Good risk | 510 (62) | 6 (13) | 504 (65) | 6 (18) | 499 (65) | 0 (0) | 5 (46) |
| Intermediate risk | 216 (26) | 33 (72) | 183 (24) | 21 (62) | 177 (23) | 12 (100) | 6 (55) |
| Poor risk | 95 (12) | 7 (15) | 88 (11) | 7 (21) | 88 (12) | 0 (0) | 0 (0) |
| Unknown/not classified | 44 | 6 | 38 | 4 | 37 | 2 | 1 |
High hyperdiploidy, 51-65 chromosomes; near haploidy, < 30 chromosomes; and low hypodiploidy, 30-39 chromosomes.
ALL indicates acute lymphoblastic leukemia; DS, Down syndrome; FISH, fluorescence in situ hybridization; iAMP21, intrachromosomal amplification of chromosome 21.
Only CRLF2-deregulated patients were tested.
Only 100 patients were screened for the presence of IGH@-CEBP and IGH@-ID4.
IKZF1 deletions were detected by MLPA (n = 4), FISH (n = 3), or both techniques (n = 12). Only 1 case was discrepant. It had a focal deletion encompassing exons 2 and 3 only and was detected by MLPA but not by FISH.
JAK2-R683G (n = 8, including all 6 DS patients), insertion mutation at 683 (n = 1), and JAK2-F694L (n = 1).
Good risk: all patients with high hyperdiploidy or ETV6-RUNX1, except those with t(9;22); poor risk: all patients with t(9;22)/BCR-ABL1, iAMP21, MLL translocations, near haploidy, low hypodiploidy, t(17;19)(q23;p13)/TCF3-HLF, abnormal 17p, and loss of 13q (except those with abnormal 17p or loss of 13q and high hyperdiploidy or ETV6-RUNX1); and intermediate risk: all other cases.