A tumor suppressor and oncogene: the WT1 story

Yang, Lin; Han, Youqi; Saiz, F Saurez; Minden, Mark D.

doi:10.1038/sj.leu.2404624

Cited by 410 publications

(385 citation statements)

References 105 publications

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“…14 WT1 is highly overexpressed in the majority of AML cases, but is also expressed, albeit at low level, in various normal tissues, such as gonads, kidney and the hematopoietic system. 15,16 On-target toxicity against these tissues has not been observed in studies of WT1-directed immunotherapy, confirming that tissues with physiological expression of WT1 are spared from immune attack. 14 Moreover, certain LAAs can be viewed as relatively leukemiaspecific, thus limiting problems associated with autoimmunity or tolerance.…”

Section: Introductionmentioning

confidence: 80%

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Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

2012

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The graft-versus-leukemia effect of allogeneic hematopoietic stem cell transplantation (HSCT) has shown that the immune system is capable of eradicating acute myeloid leukemia (AML). This knowledge, along with the identification of the target antigens against which antileukemia immune responses are directed, has provided a strong impetus for the development of antigen-targeted immunotherapy of AML. The success of any antigen-specific immunotherapeutic strategy depends critically on the choice of target antigen. Ideal molecules for immune targeting in AML are those that are: (1) leukemia-specific; (2) expressed in most leukemic blasts including leukemic stem cells; (3) important for the leukemic phenotype; (4) immunogenic; and (5) clinically effective. In this review, we provide a comprehensive overview on AML-related tumor antigens and assess their applicability for immunotherapy against the five criteria outlined above. In this way, we aim to facilitate the selection of appropriate target antigens, a task that has become increasingly challenging given the large number of antigens identified and the rapid pace at which new targets are being discovered. The information provided in this review is intended to guide the rational design of future antigen-specific immunotherapy trials, which will hopefully lead to new antileukemia therapies with more selectivity and higher efficacy.

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Section: Introductionmentioning

confidence: 80%

“…48 A similar observation has been recently made for MUC1. 49 Finally, accumulating evidence also suggests a critical role for the downregulation of WT1 in the process of myeloid differentiation (reviewed in Yang et al 15 and Sugiyama et al 16 ).…”

Section: Differentiationmentioning

confidence: 99%

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

2012

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“…Several examples, such as Myc 33 or WT1 (ref. 34) gene products that act as both tumor suppressors and oncogenes, support this idea. These results underscore the importance of assessing mutations based on their effects on signaling networks and of developing novel classification methods to do so.…”

Section: Implications For Cancer Researchmentioning

confidence: 89%

Navigating cancer network attractors for tumor-specific therapy

et al. 2012

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“…Nephroblastoma (Wilms tumor), a malignant embryonal neoplasm of the kidney, shows various histologic components with diverse cells that may express variable degrees of differentiation that represent various stages in normal or abnormal nephrogenesis [14]. The discovery of the WT1 as the causative gene in an autosomal-recessive condition identified it as a tumor suppressor gene; however, this view is not in keeping with the frequent finding of wildtype, full-length WT1 in human leukemia, breast cancer, prostate cancer, and several other cancers including most Wilms tumors [15]. In fact, the study of both the WT1 mRNA expression levels and the intensity of staining of WT1 protein in normal thyroid tissue and thyroid tumors indicates an important role of the wild-type WT1 gene in the tumorigenesis of primary thyroid cancer [16].…”

Section: Discussionmentioning

confidence: 99%

Follicular thyroid carcinoma with an unusual glomeruloid pattern of growth

et al. 2008

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SummaryWe describe an uncommon thyroid tumor in a 56-year-old woman. The widely infiltrating, angioinvasive neoplasm, 5 cm in diameter, exhibited a peculiar architectural growth pattern characterized by follicles with round to oval epithelial tufts growing within, often supported by a fibrovascular core mimicking the renal glomerulus. Colloid-empty follicles, tubular or elongated, were lined by pseudostratified tall, columnar cells with clear cytoplasm. Nuclei were round to oval, with evenly distributed, slightly coarse chromatin. Tumor cells were positive for thyroid transcription factor-1, thyroperoxidase, thyroglobulin, cytokeratin 18, Hector Battifora mesothelial cell, and vimentin. Scattered cells positive for S100, Wilms tumor 1 (WT1), and cytokeratins AE1/AE3 were found, with no reaction detected for cytokeratins 34βE12, 5/6, 7, 19, or 20. There were PAX8-PPARγ rearrangement and N-RAS mutation. No mutations were found for APC or BRAF genes, nor were RET/PTC rearrangements detected. Because of the distinctive histologic features, we propose naming this tumor follicular thyroid carcinoma with an unusual glomeruloid pattern of growth.

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A tumor suppressor and oncogene: the WT1 story

Cited by 410 publications

References 105 publications

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia

Navigating cancer network attractors for tumor-specific therapy

Follicular thyroid carcinoma with an unusual glomeruloid pattern of growth

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