A phase 2 trial of all-trans-retinoic acid in combination with interferon-α2a in children with recurrent neuroblastoma or Wilms tumor: A Pediatric Oncology Branch, NCI and Children's Oncology Group Study

2007 ◽  
Vol 49 (5) ◽  
pp. 661-665 ◽  
Author(s):  
Peter C. Adamson ◽  
Katherine K. Matthay ◽  
Michelle O'Brien ◽  
Gregory H. Reaman ◽  
Judith K. Sato ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Pediatric Oncology ◽  
Wilms Tumor ◽  
Phase 2 ◽  
Oncology Group ◽  
Oncology Group Study ◽  
Phase 2 Trial ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Interferon Α2a

Expression of the Wilms’ Tumor 1 (WT1) Gene Renders Acute Promyelocytic Leukemia Cells Resistant to All-Trans-Retinoic-Acid-Induced Differentiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4385-4385
Author(s):  
Aschwin L. Menke ◽  
Ruth H.J.N. Knops ◽  
Jurgen A.F. Marteijn ◽  
Willemijn Wissink ◽  
Josie Smeets ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Wilms Tumor ◽  
Promyelocytic Leukemia ◽  
Induced Differentiation ◽  
Expression Levels ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Wilms Tumor 1

Abstract Acute myeloid leukemia is characterized by the uncontrolled proliferation of immature cells that have lost their ability to differentiate. In the case of acute promyelocytic leukemia (AML-M3), the cells can be forced to differentiate by pharmacological dosages of all-trans retinoic acid (ATRA), a phenomenon that is successfully used in the treatment of APL patients. About 70% of the patients, suffering from PML-RARa -positive acute promyelocytic leukemia, can be cured with a combination of ATRA and anthracycline - based chemotherapy. However, relapse remains a major problem. The molecular mechanisms by which the retinoic acid receptors mediate their biological functions have been studied extensively and although various retinoic acid-responsive genes have been identified, the target genes that are crucially involved in leukemogenesis are unknown. The Wilms’ Tumor 1 gene, has been implicated in the development of leukemia. WT1 overexpression can be detected in most acute leukemias and is particularly highly expressed in APL cells. Several groups have found an inverse correlation between the expression levels of WT1 and the overall survival of leukemia patients. The underlying mechanism, however, remains to be elucidated. We have shown that the Wilms’ Tumor 1 (WT1) is strongly downregulated in APL cells, during ATRA-induced differentiation. Using a newly developed realtime RT-PCR method we have found that the expression levels of all four major WT1 isoforms are downregulated. To study the biological activity of each WT1-isoform, we have retrovirally transduced the APL cell line NB4, with the 4 major WT1 isoforms and analyzed the effect on ATRA-induced differentiation. Using flowcytometry and NBT staining, we show that ectopic expression of the different WT1-isoform inhibited ATRA-induced differentiation and subsequently, the apoptosis of APL cells, albeit with different potential. WT1-transduced cells survived pharmacological dosages of ATRA for more than 14 days and in some cases even continued to grow. These data indicate that downregulation of WT1 is essential for ATRA-induced differentiation of APL cells and provide an explanation why AML patients with high WT1 expression levels have worse overall survival in comparison to patients with low WT1 expression levels.

Rhabdomyomatous differentiation in primary Wilms tumor and hepatic metastases after chemotherapy and all-trans-retinoic acid in combination with interferon-α

2011 ◽  
Vol 57 (4) ◽  
pp. 698-699
Author(s):  
Yu-Hua Chao ◽  
Han-Ping Wu ◽  
I-Ping Chiang ◽  
Ching-Tien Peng ◽  
Yung-Li Yang ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Wilms Tumor ◽  
Hepatic Metastases ◽  
Interferon Α ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
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