Analysis of the FLT3 gene mutations in hematologic malignancies
| No. of analysis . | D835 mutation . | ITD . | |||
|---|---|---|---|---|---|
| (N) . | (%) . | Mutation type and number . | (N) . | (%) . | |
| AML | |||||
| M0 4 | 1 | (25) | Y: 1 | 0 | (0) |
| M1 63 | 2 | (3.1) | Y: 2 | 16 | (25.4) |
| M2 99 | 3 | (3.0) | Y: 3 | 10 | (10.1) |
| M3 141 | 11 | (7.8) | Y: 7, V: 2, E: 1, Y&E*: 1 | 23 | (16.3) |
| M4 70 | 4 | (5.7) | Y: 4 | 19 | (27.1) |
| M5 40 | 9 | (22.5) | Y: 5, V: 3, H: 1 | 10 | (25.0) |
| M6 6 | 0 | (0) | 1 | (16.7) | |
| M7 6 | 0 | (0) | 2 | (33.3) | |
| Total 429 | 30 | (7.0) | Y: 22, V: 5, E: 1, H: 1, Y&E: 1 | 81 | (18.9) |
| MDS | |||||
| RAEB 6 | 0 | (0) | 0 | (0) | |
| RAEB in T 13 | 1 | (7.7) | I836L + D†: 1 | 1 | (7.7) |
| CMMoL 10 | 0 | (0) | 0 | (0) | |
| Total 29 | 1 | (3.4) | I836L + D: 1 | 1 | (3.4) |
| CML-BC 11 | 0 | (0) | 0 | (0) | |
| ALL 36 | 1 | (2.8) | N: 1 | 0 | (0) |
| ATL 14 | 0 | (0) | 0 | (0) | |
| ML 17 | 0 | (0) | 0 | (0) | |
| CLL 10 | 0 | (0) | 0 | (0) | |
| MM 40 | 0 | (0) | 0 | (0) | |
| ET 3 | 0 | (0) | 0 | (0) | |
| Normal 30 | 0 | (0) | 0 | (0) | |
| No. of analysis . | D835 mutation . | ITD . | |||
|---|---|---|---|---|---|
| (N) . | (%) . | Mutation type and number . | (N) . | (%) . | |
| AML | |||||
| M0 4 | 1 | (25) | Y: 1 | 0 | (0) |
| M1 63 | 2 | (3.1) | Y: 2 | 16 | (25.4) |
| M2 99 | 3 | (3.0) | Y: 3 | 10 | (10.1) |
| M3 141 | 11 | (7.8) | Y: 7, V: 2, E: 1, Y&E*: 1 | 23 | (16.3) |
| M4 70 | 4 | (5.7) | Y: 4 | 19 | (27.1) |
| M5 40 | 9 | (22.5) | Y: 5, V: 3, H: 1 | 10 | (25.0) |
| M6 6 | 0 | (0) | 1 | (16.7) | |
| M7 6 | 0 | (0) | 2 | (33.3) | |
| Total 429 | 30 | (7.0) | Y: 22, V: 5, E: 1, H: 1, Y&E: 1 | 81 | (18.9) |
| MDS | |||||
| RAEB 6 | 0 | (0) | 0 | (0) | |
| RAEB in T 13 | 1 | (7.7) | I836L + D†: 1 | 1 | (7.7) |
| CMMoL 10 | 0 | (0) | 0 | (0) | |
| Total 29 | 1 | (3.4) | I836L + D: 1 | 1 | (3.4) |
| CML-BC 11 | 0 | (0) | 0 | (0) | |
| ALL 36 | 1 | (2.8) | N: 1 | 0 | (0) |
| ATL 14 | 0 | (0) | 0 | (0) | |
| ML 17 | 0 | (0) | 0 | (0) | |
| CLL 10 | 0 | (0) | 0 | (0) | |
| MM 40 | 0 | (0) | 0 | (0) | |
| ET 3 | 0 | (0) | 0 | (0) | |
| Normal 30 | 0 | (0) | 0 | (0) | |
Both D835 and ITD mutations are essentially restricted to AML. The D835Y mutation was most frequently found (22 of the 32 D835 mutations), followed by the D835V (5 of 32), D835H (1 of 32), D835E (1 of 32), and D835N (1 of 32) mutation.
AML indicates acute myeloid leukemia; MDS, myelodysplastic syndrome; RAEB, refractory anemia with excess of blast; RAEB in T, refractory anemia with excess of blast in transformation; CMMoL, chronic myelomonocytic leukemia; CML-BC, chronic myeloid leukemia in blast crisis; ALL, acute lymphocytic leukemia; ATL, adult T-cell leukemia; ML, malignant lymphoma; CLL, chronic lymphocytic leukemia; MM, multiple myeloma; ET, essential thrombocytosis.
D835Y and D835E mutations were found in one AML (M3) patient; cloning analysis showed that these mutations occurred in different alleles.
This mutation consisted of the insertion of three nucleotides (TTG) between D835 and I836, and AT to GA substitutions at the first and second nucleotides of I836, resulting in insertion of Leu and an Ile to Asp amino acid change (I836L + D).