Table 1 Clinico-biological features of 54 AML patients included in the study
UPNa | XL102 IC50 (μM) | de novo/Relapsed Refractory | Age/ Gender | %Blasts (BM)b | Karyotyping at diagnosis | FISH at diagnosis | Mutations identified |
|---|---|---|---|---|---|---|---|
1 | 0.22 | de novo | 34/M | 58 | ND | Tri-tetrasomy of chromosome 21/3–4 copies of RUNX1 allele in 90% cells | Monoallelic CEBPA |
2 | 0.31 | de novo | 53/M | 40 | ND | inv(16)/t(16;16) in 90% cells | Not detected |
3 | 0.95 | de novo | 22/M | 92 | ND | No abnormalities detected | FLT3-ITD |
4 | 0.49 | de novo | 29/M | 88 | 46,XY,t(9;11)(p21;q23)[12]/ 46,XY[13] | Partial deletion of MLL in 92% cells (Positive for KMT2A rearrangement:t(9;11)(p21;q23)) | NRAS c.35G > A |
5 | 0.03 | de novo | 37/M | 55 | ND | RUNX1-RUNX1T1 fusion: t(8;21) in 98% cells | NRAS c.34G > T |
6 | 0.34 | Relapsed | 45/M | 99 | ND | No abnormalities detected | Biallelic CEBPA |
7 | 0.02 | de novo | 27/F | 38 | 46,XX[15] | No abnormalities detected | Not detected |
8 | 0.02 | de novo | 35/F | 75 | 46,XX[20] | No abnormalities detected | FLT3-ITD |
9 | 0.18 | Refractory | 49/F | 59 | ND | MLL rearrangement in 94% cells | Not detected |
10 | 0.26 | de novo | 25/M | 96 | 46,XY[20] | 3 copies of RUNX1 allele/ trisomy 21 in 95% cells and 3 copies of RUNX1T1/ trisomy 8 in 15% cells | Biallelic CEBPA |
11 | 0.08 | de novo | 61/F | 42 | ND | No abnormalities detected | Not done |
12 | 0.01 | Refractory | 23/F | 78 | ND | No abnormalities detected | Not done |
13 | 0.12 | de novo | 41/F | 82 | ND | del(5q) in 94% cells, tri-tetrasomy of 11 in 80% cells and TP53 deletion in 90% cells | Not done |
14 | 0.47 | de novo | 23/M | 75 | 45,X,-Y,t(8;21)(q22;q22)[10] | RUNX1-RUNX1T1fusion: t(8;21) in 90% cells | Not done |
15 | 0.31 | Refractory | 39/M | 80 | ND | No abnormalities detected | Not done |
16 | 0.14 | de novo | 49/F | 48 | 46,XX[11] | No abnormalities detected | ASXL1 c.2113G > T, EZH2 c.1562G > A |
17 | 0.16 | de novo | 45/F | 40 | 46,XX[12] | No abnormalities detected | NPM1 Type A, IDH1 c.394C > T, NRAS c.99 T > A |
18 | 0.21 | de novo | 23/M | 65 | ND | No abnormalities detected | WT1 c.1154_1155insACTCTTGTAG, RAD21 c.374dup, NPM1 Type A, TET2 c.3646C > T, FLT3 c.2503G > T |
19 | 0.44 | de novo | 22/F | 90 | ND | RUNX1-RUNX1T1 fusion: t(8;21) in 98% cells | NRAS c.38G > A, CSF3R c.1853C > T |
20 | 0.58 | Relapsed | 39/M | 70 | ND | No abnormalities detected | IDH2 c.515G > A, RUNX1 c.808_811dup4 |
21 | 0.10 | de novo | 35/M | 45 | 49,XY, + 6, + 8,inv(16)(p13.3q22), + 21[7]/48,XY, + 4, + 8,inv(16))(p13.3q22)[3]/46,XY[1] | CBFB rearrangement: inv(16)/t(16;16) in 90% cells, trisomy 8 and trisomy 21 in 90% cells | KIT c.2446G > T, NRAS c.182A > G |
22 | 0.35 | de novo | 49/F | 64 | 46,XX[19] | No abnormalities detected | NPM1 Type A, IDH1 c.395G > A, NRAS c.38G > A |
23 | 0.008 | de novo | 35/F | 85 | ND | No abnormalities detected | NPM1 Type B, FLT3-ITD, |
24 | 0.30 | de novo | 38/F | 73 | ND | No abnormalities detected | EZH2 c.1846G > A, SMC1A c.287G > A, IDH1 c.394C > T, NRAS c.35G > A |
25 | 0.79 | de novo | 48/M | 57 | 45,X,-Y,t(8;21)(q22;q22)[5]/46,XY[9] | RUNX1/RUNX1TI fusion: t(8;21)(q22;q22) in 95% cells | KIT c.2466 T > G, KIT c.1252_1253insCTTTCT, |
26 | 0.25 | de novo | 56/M | 70 | ND | No abnormalities detected | NPM1 c.858_859insTCTG, FLT3-ITD, IDH2 c.419G > A |
27 | 0.49 | de novo | 34/M | 81 | ND | RUNX1/RUNX1TI fusion: t(8;21)(q22;q22) in 96% cells | KIT c.2466 T > G (32.12%) |
28 | 0.69 | de novo | 45/F | 85 | 46,XX[20] | No abnormalities detected | NPM1 Type A, DNMT3A c.2172C > A, IDH2 c.419G > A, FLT3 c.2506_2508delATC, KRAS c.35G > T |
29 | 0.60 | de novo | 41/F | 70 | 46,XX[20] | No abnormalities detected | NPM1 Type A, IDH1 c.394C > A, NRAS c.181C > A, TET2 c.3583A > G |
30 | 0.51 | Refractory | 34/M | 89 | 46,XY[25] | del(7q) in 10% cells. 3 copies of MLL allele due to structural rearrangement of 11q region in 15% cells | DNMT3A c.2645G > A, IDH1 c.394C > T, NRAS c.35G > A |
31 | 0.24 | de novo | 20/M | 85 | 47,XY, + 4,t(8;21)(q22;q22)[5]/46,XY,t(8;21)(q22;q22)[9]/46,XY[1] | RUNX1/RUNX1TI fusion: t(8;21)(q21.3;q22) in 90% cells | KIT c.2447A > T |
32 | 0.56 | de novo | 32/F | 96 | ND | No abnormalities detected | NPM1 Type A, TET2 c.3461G > A, FLT3-ITD |
33 | 0.12 | de novo | 47/F | 32 | ND | No abnormalities detected | Not done |
34 | 0.05 | de novo | 40/M | 74 | ND | No abnormalities detected | Not done |
35 | 0.84 | de novo | 26/F | 69 | ND | No abnormalities detected | Not done |
36 | 0.36 | Refractory | 38/F | 92 | ND | Monosomy 7 in 97% cells | Not detected |
37 | 0.92 | de novo | 22/M | 35 | 46,XY [19] | No abnormalities detected | Not detected |
38 | 0.13 | Refractory | 44/F | 80 | ND | No abnormalities detected | Not done |
39 | 0.20 | Refractory | 33/F | 68 | 46,XX,t(8;21)(q22;q22)[9]/46,XX[2] | RUNX1-RUNX1T1 fusion: t(8;21) in 94% cells | FLT3-ITD |
40 | 0.33 | Relapsed | 31/M | 60 | 46,XY [14]. Abnormal clone not proliferated | RUNX1-RUNX1T1 fusion: t(8;21) in 96% cells | Not detected |
41 | 0.16 | de novo | 52/F | 60 | ND | RUNX1-RUNX1T1fusion: t(8;21) in 96% cells | Not done |
42 | 0.86 | de novo | 36/M | 70 | 46,XY[20] | No abnormalities detected | RUNX1 c.849dupT, IDH1 c.394C > T, DNMT3A c.2644C > T, TET2 c.4210C > T,SF3B1 c.1078A > G |
43 | 0.004 | Relapsed | 46/M | 74 | 46,XY [15]. Abnormal clone not proliferated | RUNX1-RUNX1T1 fusion: t(8;21) in 94% cells | Not detected |
44 | 0.36 | de novo | 33/F | 89 | ND | No abnormalities detected | Not done |
45 | 0.31 | de novo | 24/M | 83 | 47,XY, + 8[18]/46,XY[2] | Trisomy in 85% of cells | FLT3-ITD |
46 | 0.61 | Refractory | 39/M | 66 | 46,XY,der(18;21)(p10;q10) + 21[30] | Trisomy 21 in 92% cells | Biallelic CEBPA, GATA2 c.953C > G |
47 | 0.83 | de novo | 61/M | 63 | 47,XY, + 11[6]/46,XY[14] [] | Trisomy 11 in 50% cells | Not done |
48 | 0.6 | de novo | 45/M | 94 | 44,X,-Y,-7[14]/45,XY,-7[2]/46,XY[1] | Monosomy 7 in 95% cells | KRAS c.35G > C, SF3B1 c.2098A > G |
49 | 0.05 | de novo | 24/M | 85 | ND | Trisomy 8 in 85% of cells | NPM1 type A; FLT3-ITD |
50 | 0.07 | de novo | 45/M | 68 | 46,XY [15] | No abnormalities detected | DNMT3A c.2644C > T, IDH2 c.515G > A, RUNX1 c.485G > A |
51 | 0.07 | de novo | 46/F | 55 | 46,XX [20] | Deletion(5q) in 70% cells | Not done |
52 | 0.10 | de novo | 40/F | 70 | 46,XX[11] | No abnormalities detected | NPM1 type A |
53 | 0.15 | de novo | 35/M | 90 | ND | No abnormalities detected | Not done |
54 | 0.09 | de novo | 56/M | 86 | 46,XY[13] | No abnormalities detected | Not done |