Cell death in MYRACLE samples induced by BH3 mimetics
Characteristics of patients’ samples . | Myeloma cell death (%) . | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Number . | Disease . | Sample . | Stage . | 1q21, 17p . | t(4;14) . | t(11;14) . | TP53 . | S63845 . | venetoclax . | S63845 + venetoclax . |
1 | MM | BM | D | x | x | 0 | 31 | 78 | ||
2 | MM | BM | D | 1q21 | x | 4 | 5 | 94 | ||
3 | MM | BM | D | t(4;14) | x | 5 | 9 | 73 | ||
4 | MM | BM | D | 1q21 | x | x | 33 | 33 | 81 | |
5 | MM | BM | D | 1q21 | t(11;14) | 98 | 12 | 99 | ||
6 | MM | BM | D | 1q21 | t(4;14) | x | 21 | 44 | 100 | |
7 | MM | BM | D | x | x | 0 | 25 | 58 | ||
8 | MM | BM | D | del17p | x | 5 | 15 | 44 | ||
9 | MM | BM | D | t(11;14) | 63 | 60 | 98 | |||
10 | MM | BM | D | del17p | x | 13 | 6 | 74 | ||
11 | MM | BM | D | x | x | 18 | 0 | 32 | ||
12 | MM | BM | D | 1q21 | x | x | 23 | 8 | 72 | |
13 | MM | BM | D | del17p | 5 | 1 | 2 | |||
14 | MM | BM | D | 1q21, del17p | t(11;14) | 14 | 85 | 90 | ||
15 | MM | BM | D | 1q21 | t(11;14) | 19 | 1 | 59 | ||
16 | MM | BM | D | x | 31 | 38 | 73 | |||
17 | MM | BM | D | 16 | 53 | 83 | ||||
18 | MM | BM | D | del17p | H193R | 0 | 51 | 95 | ||
19 | MM | BM | D | x | 0 | 0 | 3 | |||
20 | MM | BM | D | x | 17 | 12 | 73 | |||
21 | MM | BM | D | t(11;14) | x | 38 | 95 | 94 | ||
22 | MM | BM | D | 1q21 | x | x | x | 30 | 12 | 44 |
23 | MM | BM | D | t(11;14) | x | 15 | 79 | 85 | ||
24 | MM | BM | D | 1q21 | x | x | 81 | 47 | 88 | |
25 | MM | BM | D | x | 0 | 21 | 66 | |||
26 | MM | BM | D | 1q21 | x | 0 | 3 | 34 | ||
27 | MM | BM | D | x | x | x | 44 | 11 | 100 | |
28 | MM | BM | D | x | 0 | 24 | 70 | |||
29 | MM | BM | D | 1q21 | x | 37 | 29 | 71 | ||
30 | MM | BM | D | 1q21, del17p | t(4;14) | x | 73 | 10 | 96 | |
31 | MM | BM | D | 1q21 | t(11;14) | 33 | 19 | 95 | ||
32 | MM | BM | D | 1q21 | t(4;14) | x | 72 | 0 | 84 | |
33 | MM | BM | P | 1q21 | 12 | 0 | 38 | |||
34 | MM | BM | P | 1q21 | t(4;14) | 28 | 10 | 98 | ||
35 | MM | BM | R | t(11;14) | 56 | 57 | 98 | |||
36 | MM | BM | R | 1q21, del17p | x | x | 24 | 86 | 90 | |
37 | MM | BM | R | t(11;14) | x | 37 | 35 | 79 | ||
38 | MM | BM | R | 0 | 0 | 83 | ||||
39 | MM | BM | R | t(4;14) | 39 | 12 | 64 | |||
40 | MM | BM | R | 1q21 | t(11;14) | x | 66 | 45 | 98 | |
41 | MM | BM | R | 1q21, del17p | t(4;14) | 21 | 5 | 26 | ||
42 | MM | BM | R | 1q21 | 30 | 0 | 70 | |||
43 | MM | BM | R | 1q21 | t(4;14) | 0 | 0 | 65 | ||
44 | MM | BM | R | x | 38 | 7 | 77 | |||
45 | MM | BM | R | 1q21 | x | x | 1 | 0 | 22 | |
46 | MM | BM | R | 1q21 | t(11;14) | x | 15 | 40 | 65 | |
47 | MM | BM | R | 1q21 | x | 49 | 25 | 91 | ||
48 | MM | BM | R | 1q21 | x | 41 | 0 | 73 | ||
49 | MM | BM | R | del17p | x | 1 | 24 | 29 | ||
50 | MM | BM | R | 1q21 | x | 6 | 17 | 59 | ||
51 | MM | BM | R | 1q21 | t(11;14) | 75 | 73 | 100 | ||
52 | MM | BM | R | 1q21 | x | 9 | 0 | 53 | ||
53 | MM | BM | R | del17p | t(11;14) | x | 61 | 81 | 96 | |
54 | MM | BM | R | 1q21 | t(4;14) | x | 29 | 27 | 92 | |
55 | MM | PE | R | 1q21 | t(4;14) | x | 12 | 0 | 57 | |
56 | MM | BM | R | 44 | 41 | 74 | ||||
57 | MM | BM | R | x | x | 0 | 18 | 83 | ||
58 | MM | BM | R | 1q21 | 2 | 87 | 96 | |||
59 | MM | BM | R | x | t(11;14) | x | 2 | 8 | 63 | |
60 | MM | BM | R | x | x | 13 | 24 | 98 | ||
61 | MM | BM | R | 1q21 | x | x | 32 | 18 | 92 | |
62 | MM | BM | R | 1q21, del17p | x | 70 | 16 | 97 | ||
63 | MM | BM | R | 1q21 | t(4;14) | 10 | 4 | 87 | ||
64 | MM | BM | R | 1q21 | t(11;14) | 54 | 56 | 86 | ||
65 | MM | BM | R | 1q21, del17p | 55 | 24 | 98 | |||
66 | MM | BM | R | t(11;14) | x | 0 | 92 | 94 | ||
67 | MM | BM | R | 1q21, del17p | x | 74 | 0 | 91 | ||
68 | MM | BM | R | t(11;14) | x | 26 | 87 | 92 | ||
69 | MM | BM | R | 1q21 | t(11;14) | x | 6 | 93 | 99 | |
70 | MM | BM | R | x | x | x | 0 | 0 | 21 | |
71 | MM | BM | R | x | x | 40 | 28 | 71 |
Characteristics of patients’ samples . | Myeloma cell death (%) . | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Number . | Disease . | Sample . | Stage . | 1q21, 17p . | t(4;14) . | t(11;14) . | TP53 . | S63845 . | venetoclax . | S63845 + venetoclax . |
1 | MM | BM | D | x | x | 0 | 31 | 78 | ||
2 | MM | BM | D | 1q21 | x | 4 | 5 | 94 | ||
3 | MM | BM | D | t(4;14) | x | 5 | 9 | 73 | ||
4 | MM | BM | D | 1q21 | x | x | 33 | 33 | 81 | |
5 | MM | BM | D | 1q21 | t(11;14) | 98 | 12 | 99 | ||
6 | MM | BM | D | 1q21 | t(4;14) | x | 21 | 44 | 100 | |
7 | MM | BM | D | x | x | 0 | 25 | 58 | ||
8 | MM | BM | D | del17p | x | 5 | 15 | 44 | ||
9 | MM | BM | D | t(11;14) | 63 | 60 | 98 | |||
10 | MM | BM | D | del17p | x | 13 | 6 | 74 | ||
11 | MM | BM | D | x | x | 18 | 0 | 32 | ||
12 | MM | BM | D | 1q21 | x | x | 23 | 8 | 72 | |
13 | MM | BM | D | del17p | 5 | 1 | 2 | |||
14 | MM | BM | D | 1q21, del17p | t(11;14) | 14 | 85 | 90 | ||
15 | MM | BM | D | 1q21 | t(11;14) | 19 | 1 | 59 | ||
16 | MM | BM | D | x | 31 | 38 | 73 | |||
17 | MM | BM | D | 16 | 53 | 83 | ||||
18 | MM | BM | D | del17p | H193R | 0 | 51 | 95 | ||
19 | MM | BM | D | x | 0 | 0 | 3 | |||
20 | MM | BM | D | x | 17 | 12 | 73 | |||
21 | MM | BM | D | t(11;14) | x | 38 | 95 | 94 | ||
22 | MM | BM | D | 1q21 | x | x | x | 30 | 12 | 44 |
23 | MM | BM | D | t(11;14) | x | 15 | 79 | 85 | ||
24 | MM | BM | D | 1q21 | x | x | 81 | 47 | 88 | |
25 | MM | BM | D | x | 0 | 21 | 66 | |||
26 | MM | BM | D | 1q21 | x | 0 | 3 | 34 | ||
27 | MM | BM | D | x | x | x | 44 | 11 | 100 | |
28 | MM | BM | D | x | 0 | 24 | 70 | |||
29 | MM | BM | D | 1q21 | x | 37 | 29 | 71 | ||
30 | MM | BM | D | 1q21, del17p | t(4;14) | x | 73 | 10 | 96 | |
31 | MM | BM | D | 1q21 | t(11;14) | 33 | 19 | 95 | ||
32 | MM | BM | D | 1q21 | t(4;14) | x | 72 | 0 | 84 | |
33 | MM | BM | P | 1q21 | 12 | 0 | 38 | |||
34 | MM | BM | P | 1q21 | t(4;14) | 28 | 10 | 98 | ||
35 | MM | BM | R | t(11;14) | 56 | 57 | 98 | |||
36 | MM | BM | R | 1q21, del17p | x | x | 24 | 86 | 90 | |
37 | MM | BM | R | t(11;14) | x | 37 | 35 | 79 | ||
38 | MM | BM | R | 0 | 0 | 83 | ||||
39 | MM | BM | R | t(4;14) | 39 | 12 | 64 | |||
40 | MM | BM | R | 1q21 | t(11;14) | x | 66 | 45 | 98 | |
41 | MM | BM | R | 1q21, del17p | t(4;14) | 21 | 5 | 26 | ||
42 | MM | BM | R | 1q21 | 30 | 0 | 70 | |||
43 | MM | BM | R | 1q21 | t(4;14) | 0 | 0 | 65 | ||
44 | MM | BM | R | x | 38 | 7 | 77 | |||
45 | MM | BM | R | 1q21 | x | x | 1 | 0 | 22 | |
46 | MM | BM | R | 1q21 | t(11;14) | x | 15 | 40 | 65 | |
47 | MM | BM | R | 1q21 | x | 49 | 25 | 91 | ||
48 | MM | BM | R | 1q21 | x | 41 | 0 | 73 | ||
49 | MM | BM | R | del17p | x | 1 | 24 | 29 | ||
50 | MM | BM | R | 1q21 | x | 6 | 17 | 59 | ||
51 | MM | BM | R | 1q21 | t(11;14) | 75 | 73 | 100 | ||
52 | MM | BM | R | 1q21 | x | 9 | 0 | 53 | ||
53 | MM | BM | R | del17p | t(11;14) | x | 61 | 81 | 96 | |
54 | MM | BM | R | 1q21 | t(4;14) | x | 29 | 27 | 92 | |
55 | MM | PE | R | 1q21 | t(4;14) | x | 12 | 0 | 57 | |
56 | MM | BM | R | 44 | 41 | 74 | ||||
57 | MM | BM | R | x | x | 0 | 18 | 83 | ||
58 | MM | BM | R | 1q21 | 2 | 87 | 96 | |||
59 | MM | BM | R | x | t(11;14) | x | 2 | 8 | 63 | |
60 | MM | BM | R | x | x | 13 | 24 | 98 | ||
61 | MM | BM | R | 1q21 | x | x | 32 | 18 | 92 | |
62 | MM | BM | R | 1q21, del17p | x | 70 | 16 | 97 | ||
63 | MM | BM | R | 1q21 | t(4;14) | 10 | 4 | 87 | ||
64 | MM | BM | R | 1q21 | t(11;14) | 54 | 56 | 86 | ||
65 | MM | BM | R | 1q21, del17p | 55 | 24 | 98 | |||
66 | MM | BM | R | t(11;14) | x | 0 | 92 | 94 | ||
67 | MM | BM | R | 1q21, del17p | x | 74 | 0 | 91 | ||
68 | MM | BM | R | t(11;14) | x | 26 | 87 | 92 | ||
69 | MM | BM | R | 1q21 | t(11;14) | x | 6 | 93 | 99 | |
70 | MM | BM | R | x | x | x | 0 | 0 | 21 | |
71 | MM | BM | R | x | x | 40 | 28 | 71 |
Mononuclear cells from the BM or PE of patients with myeloma were cultured for 24 hours with 25 nM S63845, 300 nM venetoclax, or their combination, and myeloma cell death was assessed using flow cytometry. Del17p, 1q21 gain, t(4,14) and t(11;14) were determined by FISH (threshold > 50% of cells). TP53 sequencing was assessed by Sanger sequencing of complementary DNA products. TP53 mutation was considered when it involved the majority of cells.
BM, bone marrow; D, diagnosis; P, progression; PE, pleural effusion; R, relapse; x, not performed.