Pt, patients; No, number; MSC, mesenchymal stromal cell; siRNA, small interfering RNA; CECA, cyclophosphamide, etoposide, carboplatin, and cytosine arabinoside; P/Q, apoptosis in proliferating and quiescent cells; WB, Western blot; % Q cells, percentage of quiescent cells over total CD34+ cells; KD, knockdown.
Pt. no. | Source | Blast (%) | BCR-ABL status | Treatments and responses | In vitro treatment and assays | % Q cells | Days of coculture with MSC | |||
Cells in which apoptosis was determined | WB/ PCR | Bcl-XL/ Mcl-1 KD | ||||||||
1 | PB | 91 | T315I, E255K | Resistant to imatinib; treated with chemotherapy and dasatinib | P/Q | Bulk/CD34+38−/ CD34+38+ | 9.4 | 6 | ||
2 | PB | 89 | T315I, E255V | Resistant to imatinib, dasatinib, nilotinib, and ponatinib | P/Q | Bulk/CD34+38− CD34+38+ | Protein/ RNA | siRNAs | 15.9 | 7 |
3 | PB | 83 | H396R | Failed imatinib, dasatinib, and nilotinib | P/Q | Bulk/CD34+38− CD34+38+ | siRNAs | 22.1 | 10 | |
4a | PB | 89 | T315I, E255B | Resistant to imatinib, nilotinib, dasatinib, and ponatinib; treated with CECA, ponatinib, and dasatinib | Bulk/CD34+38− CD34+38+ | Protein/ RNA | siRNAs | |||
5 | PB | 80 | No mutation | Resistant to imatinib and dasatinib | Bulk | Protein/ RNA | ||||
6 | BM | 93 | No mutation | Failed imatinib; treated with nilotinib | Bulk/CD34+38− CD34+38+ | |||||
4b | PB | 62 | T315I, E255V | Resistant to imatinib, dasatinib, and ponatinib; treated with nilotinib, decitabine, and dasatinib | P/Q | 7.7 | 6 | |||
7 | PB | 24 | No mutation | Resistant to imatinib; treated with nilotinib | P/Q | 6.8 | 8 | |||
8 | PB | 11 | No mutation | Resistant to imatinib, dasatinib, nilotinib, and ponatinib; treated with decitabine, dasatinib, and bosutinib | P/Q | 14.4 | 7 |