Early cell-cycle gene expression in T-cells after hematopoietic stem cell transplantation

Regeneration of the immune system after hematopoietic stem cell transplantation (HSCT) is a slow process. Early cell cycle proto-oncogenes are key players in the first events of the proliferative process of T-cell immune response. To identify the causes of the prolonged immuno-suppression after transplantation we evaluated the expression of early T-cell cycle genes c-myc, c-jun and c-fos in peripheral blood T-cells from post-transplant patients versus healthy controls before and after phytohemagglutinin (PHA) incubation. Results show that c-jun and c-fos expression continued to increase during the first 18 months post-transplant, and eventually decreased at two years post-transplant. C-myc, c-jun and c-fos expression values also showed a time-dependent increase in surviving patients. In non-surviving patients, however, there was a time-dependent decrease in gene expression. Significant correlation was shown in c-jun expression values of all patients up to 2 years post transplant between resting state and 3h post-PHA incubation when compared to healthy controls. A positive correlation was found in c-fos gene expression between values at resting state and 3h post PHA incubation in patients with Graft versus Host Disease (GVHD) compared patients with no GVHD or healthy controls. A positive correlation was observed between white blood cell count and c-fos expression among non-surviving patients and patients who suffered from GVHD. Our results show that molecular monitoring of the immune reconstitution using c-jun, and c-fos expression combined with clinical parameters may improve the early detection of immune-function failure. This follow-up system may allow for the development of more efficient treatments and new interventions designed to hasten desirable T-cell regeneration.