The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation.

The DNA binding property of PML/RARA but not the integrity of PML nuclear bodies is indispensable for leukemic transformation.

Blog Article

PML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL).It suppresses genes expression by recruitment of a number of transcriptional repressors, resulting in differentiation block and malignant transformation of hematopoietic cells.Here, we found that mice primary hematopoietic progenitor cells (HPCs), transduced by DNA-binding-defective PML/RARA mutants, were deficient in colony formation.

Further Military Helicopter Kit experiments showed that DNA-binding-defective PML/RARA mutants could not repress the transcription of retinoic acid regulated genes.Intriguingly, there were no significant differences of the micro-speckled intracellular distribution between the mutants and wild-type PML/RARA.Some retinoic acid target genes regulated by PML/RARA are involved in not only differentiation block but also hematopoietic cell self-renewal.

Altogether, our data demonstrate that direct DNA-binding is essential for PML/RARA to immortalize hematopoietic cells, while disruption of PML-nuclear body does not seem to be 7-OH a prerequisite for hematopoietic cell transformation.