Restoration of CCAAT enhancer binding protein α P42 induces myeloid differentiation and overcomes all-trans retinoic acid resistance in human acute promyelocytic leukemia NB4-R1 cells.

摘要: All-trans retinoic acid (ATRA) is one of the first line agents in differentiation therapy for acute promyelocytic leukemia (APL). However, drug resistance a major problem influencing efficacy ATRA. Identification mechanisms ATRA are urgenly needed. In present study, we found that expression C/EBPα, an important transcription factor myeloid differentiation, was significantly suppressed resistant APL cell NB4-R1 compared with sensitive NB4 cells. Moreover, two forms C/EBPα were unequally Suppression full-length form P42 more pronounced than truncated P30. Inhibition PI3K/Akt/mTOR pathway also observed reduced by PI3K inhibitor LY294002 and mTOR RAD001 cells, suggesting inactivation responsible suppression We restored P30 lentivirus vectors respectively, P42, but not P30, could increase CD11b, CD14, G-CSFR GM-CSFR expression, which indicated occurrence differentiation. Further upregulating CD11b differential morphological changes cells after treatment. be induced infected expressing or control vector. Thus, inferred sensitivity enhanced restoration P42. addition, used histone deacetylase trichostatin (TSA) to restore Similar enhancement growth arrest detected. Together, study demonstrated inhibition impaired Restoring attractive approach APL.