World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access |
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc |
Journal website https://www.wjon.org |
Original Article
Volume 14, Number 6, December 2023, pages 488-498
Prevalence and Prognosis of Secondary Genetic Aberrations Among Patients With Core Binding Factor Acute Myeloid Leukemia: A Mitelman Database Analysis
Figures
Tables
Variable | Overall (n = 193), n (%) | inv(16) (n = 76), n (%) | t(8;21) (n = 117), n (%) | P value |
---|---|---|---|---|
aMedian (IQR). bPearson’s Chi-squared test. cWilcoxon rank sum test. dFisher’s exact test. del(7): deletion of chromosome 7; del(9): deletion of chromosome 9; t(9;22): chromosomal translocation t(9;22); +8: trisomy 8; +22: trisomy 22; -X: loss of chromosome X; -Y: loss of chromosome Y; BCR-ABL1: BCR-ABL1 fusion gene mutation; BRCC3: BRCA1/BRCA2-containing complex 3 gene mutation; NRAS: neuroblastoma RAS viral gene mutation; KRAS: Kirsten rat sarcoma virus gene mutation; KIT: receptor tyrosine kinase gene KIT mutation; CCND1: cyclin D1 gene mutation; CCND2: cyclin D2 gene mutation; ASXL1: ASXL transcriptional regulator 1 gene mutation; ASXL2: ASXL transcriptional regulator 2 gene mutation; FLT3: FMS-like tyrosine kinase 3 gene mutation; CBF-AML: core binding factor acute myeloid leukemia; AML: acute myeloid leukemia. | ||||
Sex | 0.404b | |||
Female | 73 (37.8) | 26 (34.2) | 47 (40.2) | |
Male | 120 (62.2) | 50 (65.8) | 70 (59.8) | |
Age at diagnosis (median) | 43.0 (25.0, 53.0)a | 40.5 (28.8, 53.2)a | 45.0 (23.0, 52.0)a | 0.748c |
Age group (years) | 0.230b | |||
Pediatric (< 18) | 31 (16.1) | 8 (10.5) | 23 (19.7) | |
Adult (18 - 64) | 142 (73.6) | 59 (77.6) | 83 (70.9) | |
Elderly (≥ 65) | 20 (10.4) | 9 (11.8) | 11 (9.4) | |
FAB classification | < 0.001d | |||
AML without maturation (M1) | 9 (4.7) | 2 (2.6) | 7 (6.0) | |
AML with maturation (M2) | 33 (17.1) | 3 (3.9) | 30 (25.6) | |
Acute promyelocytic leukemia (M3) | 1 (0.5) | 0 (0.0) | 1 (0.9) | |
Acute myelomonocytic leukemia (M4) | 20 (10.4) | 18 (23.7) | 2 (1.7) | |
Acute monoblastic or monocytic leukemia (M5) | 2 (1.0) | 1 (1.3) | 1 (0.9) | |
AML not otherwise specified (NOS) | 128 (66.3) | 52 (68.4) | 76 (65.0) | |
Chromosome number | < 0.001b | |||
< 46 | 54 (28.0) | 0 (0.0) | 54 (46.2) | |
46 | 112 (58.0) | 55 (72.4) | 57 (48.7) | |
> 46 | 27 (14.0) | 21 (27.6) | 6 (5.1) | |
Structural chromosome rearrangements | 50 (25.9) | 22 (28.9) | 28 (23.9) | 0.437b |
del(7) | 6 (3.1) | 4 (5.3) | 2 (1.7) | 0.214d |
del(9) | 12 (6.2) | 0 (0.0) | 12 (10.3) | 0.004d |
t(9;22) | 9 (4.7) | 8 (10.5) | 1 (0.9) | 0.003d |
Numerical chromosome abnormalities | 79 (40.9) | 21 (27.6) | 58 (49.6) | 0.002b |
+8 | 12 (6.2) | 10 (13.2) | 2 (1.7) | 0.002d |
+22 | 10 (5.2) | 10 (13.2) | 0 (0.0) | < 0.001d |
-X | 11 (5.7) | 0 (0.0) | 11 (9.4) | 0.004d |
-Y | 42 (21.8) | 0 (0.0) | 42 (35.9) | < 0.001b |
Secondary genetic mutations | 106 (54.9) | 40 (52.6) | 66 (56.4) | 0.606b |
BCR-ABL1 | 12 (6.2) | 12 (15.8) | 0 (0.0) | < 0.001d |
BRCC3 | 8 (4.1) | 0 (0.0) | 8 (6.8) | 0.023d |
NRAS | 8 (4.1) | 4 (5.3) | 4 (3.4) | 0.714d |
KRAS | 2 (1.0) | 2 (2.6) | 0 (0.0) | 0.154d |
KIT | 41 (21.2) | 17 (22.4) | 24 (20.5) | 0.758b |
CCND1 | 3 (1.6) | 0 (0.0) | 3 (2.6) | 0.280d |
CCND2 | 10 (5.2) | 0 (0.0) | 10 (8.5) | 0.007d |
ASXL1 | 11 (5.7) | 1 (1.3) | 10 (8.5) | 0.053d |
ASXL2 | 11 (5.7) | 0 (0.0) | 11 (9.4) | 0.004d |
FLT3 | 11 (5.7) | 5 (6.6) | 6 (5.1) | 0.755d |
Relapse | 134 (69.4) | 61 (80.3) | 73 (62.4) | 0.008b |
Status | 0.266b | |||
Alive | 143 (74.1) | 53 (69.7) | 90 (76.9) | |
Dead | 50 (25.9) | 23 (30.3) | 27 (23.1) | |
Overall survival (months) | 28.8 (12.0, 60.0)a | 23.2 (10.0, 50.6)a | 36.0 (16.8, 60.0)a | 0.009c |
Variable | Overall (n = 193), n (%) | del(7) (n = 6), n (%) | del(9) (n = 12), n (%) | t(9;22) (n = 9), n (%) | +8 (n = 12), n (%) | +22 (n = 10), n (%) | -X (n = 11), n (%) | -Y (n = 42), n (%) |
---|---|---|---|---|---|---|---|---|
aMedian (IQR). bFisher’s exact test. cWilcoxon rank sum test. dPearson’s Chi-squared test. del(7): deletion of chromosome 7; del(9): deletion of chromosome 9; t(9;22): chromosomal translocation t(9;22); +8: trisomy 8; +22: trisomy 22; -X: loss of chromosome X; -Y: loss of chromosome Y; CBF-AML: core binding factor acute myeloid leukemia. | ||||||||
CBF-AML group | ||||||||
inv(16) | 76 (39.4) | 4 (66.7) | 0 (0.0) | 8 (88.9) | 10 (83.3) | 10 (100.0) | 0 (0.0) | 0 (0.0) |
t(8;21) | 117 (60.6) | 2 (33.3) | 12 (100.0) | 1 (11.1) | 2 (16.7) | 0 (0.0) | 11 (100.0) | 42 (100.0) |
P value | 0.214b | 0.004b | 0.003b | 0.002b | < 0.001b | 0.004b | < 0.001d | |
Sex | ||||||||
Female | 73 (37.8) | 2 (33.3) | 4 (33.3) | 3 (33.3) | 5 (41.7) | 4 (40.0) | 11 (100.0) | 0 (0.0) |
Male | 120 (62.2) | 4 (66.7) | 8 (66.7) | 6 (66.7) | 7 (58.3) | 6 (60.0) | 0 (0.0) | 42 (100.0) |
P value | > 0.999b | > 0.999b | > 0.999b | > 0.999b | > 0.999b | < 0.001b | < 0.001d | |
Age at diagnosis (median) | 43.0 (25.0, 53.0)a | 43.5 (28.8, 50.0)a | 29.0 (19.0, 47.2)a | 38.0 (31.0, 49.0)a | 39.0 (29.8, 49.5)a | 43.5 (18.5, 47.8)a | 50.3 (37.0, 56.0)a | 42.5 (25.0, 50.3)a |
P value | 0.941c | 0.298c | 0.830c | 0.697c | 0.532c | 0.307c | 0.277c | |
Age group (years) | ||||||||
Pediatric (< 18) | 31 (16.1) | 1 (16.7) | 2 (16.7) | 0 (0.0) | 2 (16.7) | 2 (20.0) | 2 (18.2) | 9 (21.4) |
Adult (18 - 64) | 142 (73.6) | 5 (83.3) | 9 (75.0) | 8 (88.9) | 9 (75.0) | 7 (70.0) | 8 (72.7) | 31 (73.8) |
Elderly (≥ 65) | 20 (10.4) | 0 (0.0) | 1 (8.3) | 1 (11.1) | 1 (8.3) | 1 (10.0) | 1 (9.1) | 2 (4.8) |
P value | > 0.999b | > 0.999b | 0.510b | > 0.999b | 0.867b | > 0.999b | 0.298b | |
Chromosome number | ||||||||
< 46 | 54 (28.0) | 0 (0.0) | 6 (50.0) | 1 (11.1) | 0 (0.0) | 0 (0.0) | 10 (90.9) | 41 (97.6) |
46 | 112 (58.0) | 4 (66.7) | 5 (41.7) | 5 (55.6) | 1 (8.3) | 0 (0.0) | 1 (9.1) | 0 (0.0) |
> 46 | 27 (14.0) | 2 (33.3) | 1 (8.3) | 3 (33.3) | 11 (91.7) | 10 (100.0) | 0 (0.0) | 1 (2.4) |
P value | 0.137b | 0.246b | 0.191b | < 0.001b | < 0.001b | < 0.001b | < 0.001d | |
Relapse | 134 (69.4) | 6 (100.0) | 10 (83.3) | 6 (66.7) | 11 (91.7) | 9 (90.0) | 7 (63.6) | 29 (69.0) |
P value | 0.180b | 0.351b | > 0.999b | 0.110b | 0.288b | 0.739b | 0.952d | |
Status | ||||||||
Alive | 143 (74.1) | 3 (50.0) | 9 (75.0) | 7 (77.8) | 7 (58.3) | 6 (60.0) | 8 (72.7) | 35 (83.3) |
Dead | 50 (25.9) | 3 (50.0) | 3 (25.0) | 2 (22.2) | 5 (41.7) | 4 (40.0) | 3 (27.3) | 7 (16.7) |
P value | 0.181b | > 0.999b | > 0.999b | 0.304b | 0.287b | > 0.999b | 0.122d | |
Overall survival (months) | 28.8 (12.0, 60.0)a | 10.5 (6.6, 25.1)a | 33.0 (26.2, 48.0)a | 22.0 (10.0, 65.0)a | 23.1 (6.2, 66.5)a | 16.0 (1.7, 28.0)a | 30.0 (26.9, 54.0)a | 48.0 (26.9, 93.5)a |
P value | 0.050c | 0.716c | 0.649c | 0.406c | 0.011c | 0.506c | 0.004c |
Variable | Univariate Cox regression | Multivariate Cox regressiona | ||||
---|---|---|---|---|---|---|
HR | 95% CI | P value | HR | 95% CI | P value | |
aAll multivariate analyses were adjusted for sex, age group and relapse. del(7): deletion of chromosome 7; +22: trisomy 22; -X: loss of chromosome X; -Y: loss of chromosome Y; NRAS: neuroblastoma RAS viral gene mutation; KIT: receptor tyrosine kinase gene KIT mutation; CBF-AML: core binding factor acute myeloid leukemia; HR: hazard ratio; 95% CI: 95% confidence interval. | ||||||
Structural chromosome rearrangements | 0.95 | 0.50 - 1.80 | 0.884 | 0.96 | 0.50 - 1.90 | 0.915 |
del(7) | 3.40 | 1.00 - 11.00 | 0.041 | 4.20 | 1.27 - 14.20 | 0.019 |
Numerical chromosome abnormalities | 0.64 | 0.36 - 1.20 | 0.139 | 0.79 | 0.42 - 1.50 | 0.456 |
+22 | 2.8 | 1.00 - 7.90 | 0.049 | 3.60 | 1.26 - 10.50 | 0.017 |
-X | 1.00 | 0.31 - 3.50 | 0.946 | 0.74 | 0.21 - 2.60 | 0.642 |
-Y | 0.54 | 0.23 - 1.30 | 0.16 | 1.10 | 0.33 - 3.80 | 0.856 |
Secondary genetic mutations | 1.20 | 0.67 - 2.10 | 0.568 | 1.10 | 0.64 - 2.00 | 0.654 |
NRAS | 4.00 | 1.20 - 13.00 | 0.025 | 3.00 | 0.86 - 10.20 | 0.084 |
KIT | 1.20 | 0.65 - 2.30 | 0.543 | 1.10 | 0.57 - 2.10 | 0.807 |