Rapid Decrease in KRT14 and TP53 mRNA Expression in the Buccal Mucosa of Patients Receiving Total-Body Irradiation for Allogeneic Stem Cell Transplantation

Abstract

The only curative treatment option for relapsed patients with acute myeloid leukemia (AML) is allogeneic stem cell transplantation. Depletion of hematopoietic stem cells and leukemic blast cells is achieved through the systemic administration of DNA damaging agents, including total-body irradiation (TBI) prior to transplantation. Since other tissues are radiosensitive, the identification of biomarkers could facilitate the management of additional toxicities. Buccal keratinocytes are readily accessible and could provide a source of cells for RNA analysis. In this study, we obtained miRNAs and mRNAs from daily buccal swabs collected from patients undergoing allogeneic stem cell transplantation. Unexpectedly, there was no prominent p53-induced mRNA or miRNA response in these samples, despite the fact that the p53 pathway is a well-characterized radiation-inducible response. Instead, the expression of mRNAs encoding p53 and cytokeratin 14 (TP53 and KRT14, respectively) decreased precipitously within hours of the first radiation treatment. These patients went on to develop oral mucositis, however, it is unclear whether TP53 and/or KRT14 expression are predictive of this adverse event. Larger scale analysis of buccal epithelial samples from patients undergoing allogeneic stem cell transplantation appears to be warranted.

Biopsy-derived oral keratinocytes – A model to potentially test for oral mucosa radiation sensitivity

“…Our test for migration and proliferation capacities allows one to estimate the radioresistance. Cells may be used for personalized models to investigate radiation-induced damage and additional cellular features [30] , [31] . Studies on the clinical relevance are presently underway, which include a larger sample size and detailed evaluation of mucositis.…”

Continuous One Year Oral Administration of the Radiation Mitigator, MMS350, after Total-Body Irradiation, Restores Bone Marrow Stromal Cell Proliferative Capacity and Reduces Senescence in Fanconi Anemia (Fanca-/-) Mice

“…Recovery from sublethal total-body irradiation (TBI) is associated with multiple delayed effects, including acceleration of age-related markers of aging (1)(2)(3)(4)(5)(6)(7)(8)(9)(10), reduction of stem cell populations in multiple organs (1,(3)(4)(5), tissue and organ failure (9-10) and carcinogenesis (11)(12). Previously reported studies have demonstrated reduction in proliferative capacity of explanted stromal cells from the marrow of TBI mice at 3 months postirradiation (12).…”