Abstract
WT1 encodes a transcription factor involved in the pathogenesis of Wilms' tumor. A high level of expression has been reported in blasts from patients with various hematological malignancies. The study was performed to evaluate the utility of monitoring WT1 expression in children with leukemia at diagnosis, during therapy, and following bone marrow transplant. We tested a total of 204 samples prospectively. These included samples from patients with the following diagnoses: acute lymphoblastic leukemia (ALL) at diagnosis (n = 45), at relapse (n = 14), and in remission (n = 45); acute non-lymphoblastic leukemia (ANLL) at diagnosis (n = 14), at relapse (n = 5), and in remission (n = 12); and chronic myelogenous leukemia (CML) in blast crisis (n = 1) and in chronic phase (n = 1). A total of 33 of these patients were transplanted: 19 ALL, 12 ANLL, and 2 CML. In addition, samples from 5 patients with aplastic anemia and 28 controls were obtained from peripheral blood (n = 17), cord blood (n = 3), and bone marrow (n = 8). Primer pairs were designed to locate specific nucleotide sequences for mRNA of WT1. RT-PCR was performed in all samples and compared with K562 cells from ATCC (defined as 1.0) as positive control. A positive test was arbitrarily defined as WT1/K562 > 0.5. Samples at diagnosis and relapse, including 56 out of 59 ALL (95%), 26 ANLL (100%), and 1 CML in blast crisis, demonstrated high levels of WT1 expression. In contrast, only 5 of 90 samples obtained in remission or post-transplant showed high levels of WT1 expression ( P < 0.0001; 95% CI = 0.66-0.94). The five patients with high WT1 expression during follow-up relapsed within 2 to 6 months. In conclusion, we have found that WT1 is consistently elevated in children with leukemia. Significant differences in the level of WT1 expression were noted between these patients during diagnosis and at relapse, and those during remission. More importantly, following bone marrow transplant, a significant high level of WT1 expression preceded clinical relapse by 2 to 6 months. Therefore, WT1 is a reliable marker for monitoring minimal residual disease during therapy as well as in the post-transplant period.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.