Table 2.
Experimental strategies for resistance.
| Author | Drug | Function | Study | Source | Result | Follow up | p | Ref |
|---|---|---|---|---|---|---|---|---|
| Takeshita, et al. | Tamibarotene (TAM) | RAR α agonist | Clinical trial | 270 Patients | RFS %: TAM 94; ATRA 84 | 7- Year | 0.027 | [102] |
| Lo Coco, et al | Gentuzumab Ozogamicin | Anti CD33 + Calicamicin | Prospective Study | 16 Patients Relapse | RFS % 43 ± 15% | 31 month | - | [104] |
| Gale, et al | CEP-701 (Lestaurtinib) | FLT3 inhibitor | In vitro | Primary APL blast (n = 6) | Greater effect on cell survival/proliferation in FLT3/ITD cells, but this inhibition was reduced in the presence of ATRA | - | - | [105] |
| Mastrangelo, et al | Ascorbate Megadose | Pro-oxidant, | In vitro | Cells Lines (n = 6) | Highly sensitive, with an average 50 % lethal concentration (LC50) of 3 mM Normal CD34+ not sensitive | - | - | [108] |
| Noguera, et al | Ascorbate Megadose | Pro-oxidant, | In vitro | Primary APL (n = 9) and AML (n = 33) Blast; Cells Lines (n = 5) | Higer sensitivity ASC induce PML/RARa and PML degradation ASC potenciate the effect of ATO Normal CD34+ not sensitive |
- | < 0.001 | [107] |
| Masciarelli, et al | Tunicamycin | Endoplasmic reticulum (ER) stress-inducing drug | In vitro | Primary APL Blast; ATRA sensitive and resistant APL cell lines | ER stress + ATO induced apoptosis in RA-sensitive an RA-resistant APL cell lines | - | < 0.005 | [114] |
| Gu, et al | pharicin B, | stabilizes RARα protein | In vitro | Primary APL Blast; ATRA sensitive and resistant APL cell lines | Induced apoptosis in RA-sensitive and RA-resistant APL cell lines | - | < 0.001 | [115] |
| Wang, et al | LG-362B, | caspases-mediated degradation of PML-RARα | In vitro e in vivo | Primary APL Blast; ATRA sensitive and resistant APL cell lines Murin models |
Inhibits the proliferation of APL in vitro and in vivo Synergistic or additive differentiation effect with ATRA Overcom ATRA resistance |
- | RTW: < 0.01 | [116] |
| Ying, et al | 2-bromopalmitate (2-Br) | inhibitor of fatty acid oxidation | In vitro | Primary APL Blast; ATRA sensitive and resistant APL cell lines Murin models |
ATRA + 2Br to overcoming ATRA resistance | - | Blast: < 0.05 to < 0.001 (n = 7); > 0.05 (n = 4) RTW: < 0.05 |
[118] |
| Ganesan et al | ATO plus Bortezomib | downregulation of the NFĸB pathway, PML-RARa degradation inhibition of the proteasome by bortezomib | In vitro e in vivo | ATO sensitive and resistant APL cell lines Murin models |
Synergistic effect in both ATO sensitive and ATO resistant APL cell lines Reduce leukemic burden and induce long-term survival in an APL mouse model |
- | OS mouse: 0.0001 | [82] |
| Hussain et al | phenylarsine oxide (PAO) | organic arsenic derivatives | In vitro | Cells Lines transfected with PLZF-RARa | PLZF-RARa degradation | - | - | [119] |
RFS: relapse-free survival, RTW: reduction tumor weight, OS: overal survival.