Strong expression of p53 protein in bone marrow samples after hematopoietic stem cell transplantation indicates risk of relapse in pediatric acute lymphoblastic leukemia patients

Abstract

Background For pediatric ALL patients that relapse or respond poorly to conventional chemotherapy treatment, HSCT is one treatment option. Still, relapse occurs in 30% of the children after HSCT. Mutations in the tumor suppressor gene TP53 which can lead to an altered p53 protein expression are rare at time of diagnosis of ALL, yet occur more frequent at relapse indicating a more aggressive disease. Our aim was to evaluate if alterations in the expression of the tumor suppressor protein p53 signaled a relapse in pediatric ALL patients post‐HSCT and could guide for preemptive immunotherapy. Procedure Paraffin‐embedded bone marrow samples from 46 children diagnosed with ALL between 1997 and 2010, and transplanted at Karolinska University Hospital, were analyzed for p53 by IHC. Samples were analyzed independently at diagnosis, before HSCT, and after HSCT 0‐3 months, 3‐6 months, and 6‐12 months. Result Strong expression of p53 in the bone marrow at 0‐3‐months after HSCT was associated with increased risk of relapse, odds ratio 2.63 (confidence interval 1.08‐6.40) P = 0.033. Conclusion Evaluation of p53 protein expression in bone marrow from pediatric ALL patients that undergo HSCT may be a potential, additional prognostic marker for predicting relapse after HSCT.

The Effects Of Stem Cell Therapy In The Treatment Of Childhood Acute Lymphoblastic Leukemia

“…Stem cell transplants may be used to replace healthy blood-forming cells after treatments of chemotherapy and total-body irradiation. Stem cells are typically used only for cases in which there is a high risk of relapse [5][6][7]. Additionally, many target therapies show promise in the treatment of childhood ALL including tyrosine kinase inhibitors, monoclonal antibody therapy, and proteasome inhibitor therapy [3].…”