Effect of antisense oligodeoxynucleotide (ASODN) to PML-RAR alpha fusion gene on acute promyelocytic leukemia cell line NB4

Objective: To study the effect of PML-RAR alpha expression on the proliferation and differentiation of NB4 cells, and explore the role of PML-RAR alpha fusion gene in the pathogenesis of acute promyelocytic leukemia (APL).

Methods: ASODN-mediated inactivation of PML-RAR alpha mRNA was measured by RT-PCR. The proliferation and differentiation of NB4 cells were determined by proliferation curve, morphology, membrane CD antigen and NBT test. NB4 cell cycle was analyzed by FACS.

Results: The inactivation of PML-RAR alpha mRNA by ASODN decreased the percentage of S phase cells (from 56% to 37%), inhibited the NB4 cell proliferation and induced NB4 cells to differentiate to morphologically and functionally mature granulocytes.

Conclusions: PML-RAR alpha gene, as a molecular marker of APL, is possibly responsible for genesis of APL.