Profiling of somatic mutations and fusion genes in acute myeloid leukemia patients with FLT3-ITD or FLT3-TKD mutation at diagnosis reveals distinct evolutionary patterns

Table 1 Clinical, cytogenetics and molecular genetics characteristic of 207 analyzed AML patients

Parameter	FLT3-ITD (n = 58)	FLT3-TKD (n = 16)	FLT3_wtAML (n = 133)	P value^a
Male	23 (39.7)	12 (75)	80 (60.2)	0.009
Age	48 (14–73)	41 (14–76)	45 (15–76)	0.367
WBC at diagnosis, × 10⁹/L	72.9 (2.3–405.1)	68.2 (1.8–251.1)	24.2 (0.57–311.0)	0.000
Blasts in BM, %	65.9 (22.0–95.6)	55.5 (30.8–94.0)	56.0 (14.4–94.5)	0.040
FAB subtype, n (%)				0.983
M0	0	0	0
M1	3 (5.2)	1 (6.3)	4 (3.0)
M2	16 (27.6)	5 (31.3)	38 (28.6)
M4	20 (34.5)	6 (37.5)	41 (30.8)
M5	14 (24.1)	4 (25.0)	36 (27.1)
M6	2 (34)	0	5 (3.8)
Unclassified	1 (1.7)	0	6 (4.5)
Secondary-AML	2 (3.4)	0	3 (2.3)
Cytogenetics, n (%) (n = 197)
Normal karyotypes	35 (64.8)	6 (40.0)	62 (48.4)	0.079
Aberrant karyotypes	19 (35.2)	9 (60.9)	66 (51.6)
Gene Mutation^c, n (%)
NPM1	28 (53.8)^&	4 (25)	20 (15.3)	0.000
DNMT3A	18 (34.6)^&	4 (25)	17(13.0)	0.003
RUNX1	1 (1.7)	1 (6.3)	8 (6.1)	0.492
KIT	3 (5.8)	0 (0)	6 (4.6)	0.623
RAS	1 (1.9)^&	1 (6.3)	27 (20.6)	0.003
PTPN11	5 (9.6)	1 (6.3)	6 (6.3)	0.435
TET2	6 (11.5)	1 (6.3)	10 (7.6)	0.656
IDH1/2	5 (19.6)	3 (18.8)	20 (15.3)	0.522
CEBPA	2 (3.8)^&	0 (0)	26 (19.8)	0.005
ASXL1	2 (3.8)	2 (12.5)	13 (9.9)	0.348
TP53	0 (0)^&	1/16 (6.3)	8 (6.1)	0.189
Methylation-related genes^b	23 (44.2)	6 (37.5)	42 (32.1)	0.297
Number of mutations	3.2 (1–7)^&	3.6 (1–6)	2.7 (0–8)	0.022
CR after two cycles of induction	29/46 (63)	10/14 (71.4)	100/113 (88.5)	0.001
Consolidation in CR1
CT SCT	16 (55.2) 13 (44.8)	5 (50) 5 (50)	6 (49.5) 47 (50.5)	0.865
Three-year OS (%)	36 ± 9.1	65.6 ± 15.1	50.6 ± 7	0.020
Three-year EFS (%)	27.2 ± 8.1	55.9 ± 16.2	40.5 ± 6.5	0.005

Italic values indicate significance of P value (P < 0.05)
WBC white blood count, BM bone marrow, FAB French–America–British, CR complete remission, CT chemotherapy, SCT stem cell transplantation
^aP-values for categorical variables are from chi-square test, P-values for continuous variables are from the ANOVA test
^bMethylation related gene included DNMT3A, IDH1/2, and TET2
^c52 FLT3-ITD, 16 FLT3-TKD and 131 FLT3 wildtype patients were analyzed for gene mutations
^#p value for frequency of favorable, intermediate and unfavorable karyotype in three groups
^&P value < 0.05 between the FLT3-ITD group and FLT3_wt group

ISSN: 2162-3619