Clinical characteristics of patients studied
Patient no. . | Age at study, y . | Sex . | BM versus PBSC . | Stage . | CD34+ cells versus MNC . | Prior inter-feron . | Months from diagnosis to study . | Months from diagnosis to imatinib . | Months on imatinib . | BCR/ABL-positive CD34+ cells detected on FISH* . | Mutations detected on initial evaluation (clones containing mutation/clones sequenced) . | Months from initial to follow-up evaluation . | Mutations detected on follow-up evaluation (clones containing mutation/clones sequenced)† . | Status at follow-up . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 64 | M | BM | CP | CD34+ | Y | 31 | 25 | 6 | Yes | M2371 (8/10) | 7 | M2371 (6/13) | CCR‡ |
| E352G (4/13) | ||||||||||||||
| V304G (3/13) | ||||||||||||||
| M351T (3/13)§ | ||||||||||||||
| 2 | 70 | M | BM | CP | CD34+ | N | 15 | 2 | 13 | Yes | G321E (9/15) | 15 | E352G (5/14) | CCR |
| E373G (2/15) | T389A (2/14) | |||||||||||||
| D276G (2/15) | ||||||||||||||
| 3 | 37 | F | BM | CP | MNC | N | 6 | 2 | 4 | NA | Y353H (2/20) | 2 | D276G (5/17) | Relapse-BC‡ |
| E352G (2/20) | ||||||||||||||
| 4 | 54 | M | PBSC | AP | CD34+ | Y | 38 | 13 | 25 | NA | L248V (6/10) | 18 | L248V (13/13) | Relapse-AP‡ |
| 5 | 66 | M | PBSC | CP | CD34+ | N | 12 | 1 | 11 | Yes | G321E (6/10) | NA | NA | NA |
| 6 | 52 | F | BM | CP | CD34+ | Y | 45 | 26 | 19 | Yes | ND (0/14) | 30 | L248V (3/10) | CCR‡ |
| V371A (2/10) | ||||||||||||||
| 7 | 67 | F | BM | CP | CD34+ | Y | 60 | 57 | 3 | Yes | ND (0/10) | 25 | G321E (11/14) | CCR‡ |
| 8 | 41 | M | BM | CP | CD34+ | N | 11 | 1 | 10 | Yes | ND (0/10) | NA | NA | CCR |
| 9 | 57 | F | BM | CP | CD34+ | Y | 60 | 56 | 4 | No | ND (0/28) | NA | NA | CCR |
| 10 | 58 | F | BM | CP | CD34+ | N | 15 | 9 | 6 | NA | ND (0/22) | 18 | ND (0/13) | CCR‡ |
| 11 | 54 | F | BM | CP | CD34+ | Y | 57 | 51 | 6 | Yes | ND (0/10) | 15 | D276G (2/14) | CCR‡ |
| 12 | 54 | F | BM | CP | CD34+ | N | 7 | 1 | 6 | NA | ND (0/12) | 16 | Y353H (10/10) | CCR‡ |
| 13 | 54 | M | BM | CP | CD34+ | N | 10 | 3 | 7 | NA | ND (0/10) | NA | NA | CCR |
Patient no. . | Age at study, y . | Sex . | BM versus PBSC . | Stage . | CD34+ cells versus MNC . | Prior inter-feron . | Months from diagnosis to study . | Months from diagnosis to imatinib . | Months on imatinib . | BCR/ABL-positive CD34+ cells detected on FISH* . | Mutations detected on initial evaluation (clones containing mutation/clones sequenced) . | Months from initial to follow-up evaluation . | Mutations detected on follow-up evaluation (clones containing mutation/clones sequenced)† . | Status at follow-up . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 64 | M | BM | CP | CD34+ | Y | 31 | 25 | 6 | Yes | M2371 (8/10) | 7 | M2371 (6/13) | CCR‡ |
| E352G (4/13) | ||||||||||||||
| V304G (3/13) | ||||||||||||||
| M351T (3/13)§ | ||||||||||||||
| 2 | 70 | M | BM | CP | CD34+ | N | 15 | 2 | 13 | Yes | G321E (9/15) | 15 | E352G (5/14) | CCR |
| E373G (2/15) | T389A (2/14) | |||||||||||||
| D276G (2/15) | ||||||||||||||
| 3 | 37 | F | BM | CP | MNC | N | 6 | 2 | 4 | NA | Y353H (2/20) | 2 | D276G (5/17) | Relapse-BC‡ |
| E352G (2/20) | ||||||||||||||
| 4 | 54 | M | PBSC | AP | CD34+ | Y | 38 | 13 | 25 | NA | L248V (6/10) | 18 | L248V (13/13) | Relapse-AP‡ |
| 5 | 66 | M | PBSC | CP | CD34+ | N | 12 | 1 | 11 | Yes | G321E (6/10) | NA | NA | NA |
| 6 | 52 | F | BM | CP | CD34+ | Y | 45 | 26 | 19 | Yes | ND (0/14) | 30 | L248V (3/10) | CCR‡ |
| V371A (2/10) | ||||||||||||||
| 7 | 67 | F | BM | CP | CD34+ | Y | 60 | 57 | 3 | Yes | ND (0/10) | 25 | G321E (11/14) | CCR‡ |
| 8 | 41 | M | BM | CP | CD34+ | N | 11 | 1 | 10 | Yes | ND (0/10) | NA | NA | CCR |
| 9 | 57 | F | BM | CP | CD34+ | Y | 60 | 56 | 4 | No | ND (0/28) | NA | NA | CCR |
| 10 | 58 | F | BM | CP | CD34+ | N | 15 | 9 | 6 | NA | ND (0/22) | 18 | ND (0/13) | CCR‡ |
| 11 | 54 | F | BM | CP | CD34+ | Y | 57 | 51 | 6 | Yes | ND (0/10) | 15 | D276G (2/14) | CCR‡ |
| 12 | 54 | F | BM | CP | CD34+ | N | 7 | 1 | 6 | NA | ND (0/12) | 16 | Y353H (10/10) | CCR‡ |
| 13 | 54 | M | BM | CP | CD34+ | N | 10 | 3 | 7 | NA | ND (0/10) | NA | NA | CCR |
BM indicates bone marrow; PBSC, peripheral blood stem cells; MNC, mononuclear cells; FISH, fluorescence in situ hybridization; CP, chronic phase; CCR, complete cytogenetic response; NA, not available; BC, blast crisis; AP, accelerated phase; ND, not detected.
FISH results for these patients were previously reported by Bhatia et al.12 Eight patients were common to the 2 studies. Of these, 5 had mutations detected in the present study, and all had BCR/ABL-positive cells detected by FISH in the previous study. BCR/ABL-positive CD34+ cells were detected by FISH in 2 of the 3 patients in whom mutations were not detected in this study
Mutation analysis on follow-up samples was performed using RNA extracted from CD34+ cells for patients 1, 2, and 3 and from MNC for patients 4, 6, 7, 10, 11, and 12
These patients had rising BCR/ABL mRNA levels on Q-PCR analysis
The V304G and M351T mutations were detected simultaneously in 3 clones