Article Figures & Data
Figures
- Figure 1.
Triptolide potently induces cell death in blast crisis CML cells independent of cellular responses to imatinib. KBM5 and KBM5STI571 cells (A) and Ba/F3vec, Ba/F3Bcr-Ablp210wt, Ba/F3Bcr-AblE255K, and Ba/F3Bcr-AblT315I cells (B) were treated with various concentrations of triptolide for 48 h. C, blasts from patients with CML were treated for 24 h. Cell death was determined by Annexin V staining.
- Figure 2.
Triptolide decreases XIAP, Mcl-1, and Bcr-Abl levels in CML cells. A, K562 cells were treated with 100 nmol/L triptolide. XIAP and Mcl-1 mRNA levels were determined at various time points by real-time reverse transcription-PCR. B, K562 cells were treated with various concentrations of triptolide for 48 h or with 100 nmol/L triptolide for various times. C, KBM5 and KBM5STI571 cells were treated with triptolide for 24 h and with imatinib for 24 to 72 h. D, cells from patients with CML were treated with triptolide for 24 h. XIAP, Mcl-1, and Bcr-Abl protein levels were determined by Western blot analysis and cell death was determined by Annexin V staining.
- Figure 3.
Combination of triptolide and imatinib enhances death in KBM5 cells. KBM5 cells were treated with triptolide for 24 h plus 1 μmol/L imatinib for an additional 24 h. Cell death was determined by Annexin V staining.
- Figure 4.
Triptolide induces the death of both quiescent and proliferating CD34+ cells from patients with CML. Left, profiles of CFSE-labeled cells from patients with CML. Shaded area, proliferation profile at the time of Annexin V assay; open area, fluorescence profile of cells before starting the culture. Cells were cultured with growth factors or cocultured with MS-5 cells for 4 to 7 d and then treated with triptolide for 24 or 48 h. Apoptosis in quiescent and proliferating CD34+ cells was determined using Annexin V staining and shown as % positivity of the respective populations. GF, growth factor; P, proliferating; Q, quiescent.
Tables
- Table 1.
Characteristics of CML patients treated with triptolide in vitro
Patient Blast (%) Sample source In vivo treatments and responses at the time of sampling Bcr-Abl mutation status Blast crisis lineage In vitro triptolide treatment IC50 (nmol/L) Western blot 1 49 Peripheral blood Resistant to imatinib and nilotinib M351T Myeloid 32.5 XIAP 2 62 Peripheral blood Resistant to imatinib Wild-type Myeloid 178.9 XIAP, Mcl-1, Bcr-Abl 3 80 Peripheral blood Resistant to imatinib, nilotinib, and other therapies Wild-type Myeloid 84.1 — 3a 83 Bone marrow Wild-type 87.9 — 4 91 Peripheral blood Hydrea, later died Wild-type Myeloid 43.0 — 5 87 Peripheral blood No cytogenetic remission with imatinib, dasatinib, or nilotinib Wild-type Myeloid 111.7 XIAP, Mcl-1, Bcr-Abl 6 64 Peripheral blood Failed imatinib and other chemotherapies Wild-type Bi-lineage 206.2 XIAP, Mcl-1, Bcr-Abl - Table 2.
Characteristics of patients with CML, whose CD34+ cells were used for testing triptolide sensitivity
Patient Source Blast (%) Treatment and responses at the time of sampling Bcr-Abl mutation status Blast crisis lineage 1 Peripheral blood 59 Resistant to or relapsed from various treatment including IFN, imatinib, dasatinib, fludarabine + ara-C bid, and i.v. homoharringtonine + imatinib F317L Myeloid 2 Peripheral blood 17 Resistant to various therapies including IFN + low-dose ara-C, imatinib, nilotinib, and dasatinib Wild-type Myeloid 3 Peripheral blood 58 Resistant to imatinib and nilotinib F317L Lymphoid 4 Peripheral blood 58 Achieved short hematologic remission with idarubicin + ara-C/imatinib but soon after had evidence of Philadelphia-positive chromosome, resistant to dasatinib and MK-0457 T315I Myeloid 5 Bone marrow 60 Achieved hematologic response with imatinib and dasatinib, achieved and then lost cytogenetic response to dasatinib, was on bosutinib V299L Myeloid
Volume 8, Issue 9
