title: Early cell-cycle gene expression in T-cells after hematopoietic stem cell transplantation.
abstract: 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.
authors.affiliation: The Institute of Medical Research, Faculty of Medicine, Hebrew University of Jerusalem, Israel; Department of Bone Marrow Transplantation, Hadassah University Hospital, Israel. Electronic address: shivtia@g.jct.ac.il.
authors.forename: Shivtia
authors.initials: S
authors.lastname: Trop-Steinberg
authors.forename: Yehudith
authors.initials: Y
authors.lastname: Azar
authors.forename: Reuven
authors.initials: R
authors.lastname: Or
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002453:Cell Cycle / Q000276:immunology*; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D014157:Transcription Factors
keywords: C-fos; C-jun; C-myc; GVHD; HSCT