Characteristics of patients and RAPA IC50 in 23 fresh AML samples
. | . | . | . | . | . | FLT3 . | . | . | |
|---|---|---|---|---|---|---|---|---|---|
| Patient no. . | Age, y . | FAB . | WBC count, cells × 109 . | AML status . | Cytogenetics . | ITD . | D835 . | Rapamycin IC50, nM, CFU-L* . | |
| 12 | 38 | 1 | 54 | Diag | 46 XY, inv(16) | - | - | > 100 | |
| 2 | 70 | t-AML | 2.5 | Diag | 46 XY, inv(3) | ND | ND | 94.4 | |
| 8 | 75 | 5 | 46.2 | Diag | 46 XX | - | - | 88.3 | |
| 23 | 53 | 1 | 1.1 | Rel | nd | - | - | 43.6 | |
| 6 | 55 | 5 | 8.4 | Rel | 46 XX | - | - | 30.3 | |
| 14 | 55 | 0 | 2.3 | Rel | 46 XY, del(5) | - | ND | 26 | |
| 9 | 63 | 3v | 12.4 | Diag | 46 XX, t(15;17) | - | + | 20.3 | |
| 10 | 13 | 1 | 73 | Diag | 47 XY +(8) | + | - | 19 | |
| 18 | 59 | 4 | 103 | Rel | 46 XX | - | ND | 12.5 | |
| 4 | 50 | 5 | 58 | Diag | 46 XY | - | - | 12 | |
| 1 | 47 | t-AML | 38 | Rel | 45 XX, inv(3), del(5) | - | - | 7.4 | |
| 13 | 57 | 1 | 24 | Diag | 46 XX | + | - | 3.36 | |
| 5 | 84 | 5 | 14.3 | Diag | 47 XX, iso (9), +(9) | - | - | 3.3 | |
| 7 | 61 | 2 | 39.5 | Diag | 46 XY | + | - | 2.8 | |
| 17 | 59 | 4 | 86 | Diag | 46 XY | + | - | 2.6 | |
| 3 | 77 | 1 | 195 | Diag | 46 XX | - | - | 1 | |
| 11 | 50 | 0 | 90 | Diag | 47 XY +(13) | - | - | 1 | |
| 21 | 69 | t-AML | 2.7 | Diag | nd | - | ND | 1 | |
| 15 | 45 | 5 | 240 | Diag | failure | + | - | < 1 | |
| 16 | 31 | 4 | 11 | Diag | 45 XY t(3;3), -(7) | - | - | < 1 | |
| 19 | 77 | 1 | 19 | Rel | 46 XX | - | ND | < 1 | |
| 20 | 56 | 1 | 26.9 | Rel | Failure | + | - | < 1 | |
| 22 | 67 | t-AML | 25 | Diag | 46 XY | - | - | < 1 | |
. | . | . | . | . | . | FLT3 . | . | . | |
|---|---|---|---|---|---|---|---|---|---|
| Patient no. . | Age, y . | FAB . | WBC count, cells × 109 . | AML status . | Cytogenetics . | ITD . | D835 . | Rapamycin IC50, nM, CFU-L* . | |
| 12 | 38 | 1 | 54 | Diag | 46 XY, inv(16) | - | - | > 100 | |
| 2 | 70 | t-AML | 2.5 | Diag | 46 XY, inv(3) | ND | ND | 94.4 | |
| 8 | 75 | 5 | 46.2 | Diag | 46 XX | - | - | 88.3 | |
| 23 | 53 | 1 | 1.1 | Rel | nd | - | - | 43.6 | |
| 6 | 55 | 5 | 8.4 | Rel | 46 XX | - | - | 30.3 | |
| 14 | 55 | 0 | 2.3 | Rel | 46 XY, del(5) | - | ND | 26 | |
| 9 | 63 | 3v | 12.4 | Diag | 46 XX, t(15;17) | - | + | 20.3 | |
| 10 | 13 | 1 | 73 | Diag | 47 XY +(8) | + | - | 19 | |
| 18 | 59 | 4 | 103 | Rel | 46 XX | - | ND | 12.5 | |
| 4 | 50 | 5 | 58 | Diag | 46 XY | - | - | 12 | |
| 1 | 47 | t-AML | 38 | Rel | 45 XX, inv(3), del(5) | - | - | 7.4 | |
| 13 | 57 | 1 | 24 | Diag | 46 XX | + | - | 3.36 | |
| 5 | 84 | 5 | 14.3 | Diag | 47 XX, iso (9), +(9) | - | - | 3.3 | |
| 7 | 61 | 2 | 39.5 | Diag | 46 XY | + | - | 2.8 | |
| 17 | 59 | 4 | 86 | Diag | 46 XY | + | - | 2.6 | |
| 3 | 77 | 1 | 195 | Diag | 46 XX | - | - | 1 | |
| 11 | 50 | 0 | 90 | Diag | 47 XY +(13) | - | - | 1 | |
| 21 | 69 | t-AML | 2.7 | Diag | nd | - | ND | 1 | |
| 15 | 45 | 5 | 240 | Diag | failure | + | - | < 1 | |
| 16 | 31 | 4 | 11 | Diag | 45 XY t(3;3), -(7) | - | - | < 1 | |
| 19 | 77 | 1 | 19 | Rel | 46 XX | - | ND | < 1 | |
| 20 | 56 | 1 | 26.9 | Rel | Failure | + | - | < 1 | |
| 22 | 67 | t-AML | 25 | Diag | 46 XY | - | - | < 1 | |
FAB indicates French-American-British classification; WBC, white blood cells; FLT3-ITD, FLT3-internal tandem duplication; FLT3-D835, FLT3 mutation in the activation loop; Diag, diagnosis; t-AML, transformed-AML (AML secondary to refractory anemia with excess blasts); ND, not done; and Rel, relapse.
Marrow AML cells were grown in methylcellulose medium supplemented with 10% 5637-CM and increasing concentrations (ie, 0, 0.1, 1, 10, and 100 nM) of RAPA. CFU-Ls were scored at day 7. RAPA IC50s were calculated after linearization of the semilogarithmic dose response curve