China
Africa
Explore chapters and articles related to this topic
Gene Expression Profiling to Detect New Treatment Targets in Leukemia and Lymphoma: A Future Perspective
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Torsten Haferlach, Wolfgang Kern, Alexander Kohlmann
However, in most cases the candidate targets identified in expression studies (28) using relapse or treatment outcome as endpoints of their observation and independent verification is missing (38). Therefore, conflicting results are largely due to differences in treatment and biology of enrolled patients. The gap between gene expression profiling to characterize biological entities in leukemia and lymphoma and the targets to be tested is still not closed, and translation from data management to drug design is still missing. However, the characterization of molecular mutations and of pathway alterations in the leukemias proceeds with high velocity as can be demonstrated by the recent study of Mullighan et al. who revealed the PAX gene as the most frequent target of molecular mutation in ALL and showed that direct disruption of pathways controlling B-cell development and differentiation contribute to B-progenitor ALL pathogenesis (39). This is just one more example of the recent progress in the identification of new molecular targets in ALL.
Rhabdomyosarcoma
Published in Dongyou Liu, Tumors and Cancers, 2017
Alveolar RMS carries specific chromosomal translocations t(2;13)(q35;q14) or t(1;13)(p36;q14) that lead to PAX3-FOXO1 or PAX7-FOXO1 fusion genes in 55% or 1–20% of cases, respectively. In addition, some cases of alveolar RMS harbor t(2;2)(q35;p23), which has similar transactivation properties as PAX3-FOTO1. The remaining alveolar RMS (20%) is PAX gene fusion-negative (PFN), and demonstrates a similar clinical course to embryonal RMS [6].
A Review of the Role of Cytogenetics in the Diagnosis of Orbital Rhabdomyosarcoma
Published in Seminars in Ophthalmology, 2019
Paula Cortes Barrantes, Frederick A. Jakobiec, Thaddeus P. Dryja
4The fusion proteins found in ARMS have a DNA-binding domain from the PAX gene and a transcriptional transactivation domain from the FOX01 gene. The fusion gene has FOX01’s high transcriptional activity, resulting in high fusion protein levels. The fusion proteins have been found to be more stable than the wild type PAX proteins. The fusion protein and the wild type PAX proteins have a similar function: they activate the genes encoding the myogenin and MyoD transcription factors. The resulting constantly high levels of myogenin and MyoD are thought to be responsible for the arrest in the maturation of the tumor cells in ARMS.16 Investigators have proposed that the fusion protein generates additional direct or indirect effects on mRNA and microRNA expression, leading to increased cell growth, the expression of proliferative transcription factors and polyploidy.17,18 In non-neoplastic myocytes, the AKT serine-threonine protein kinase is able to inhibit the FOX01 protein by phosphorylation; however, for this to occur, the protein must move to the cytoplasmic compartment. The PAX3 or PAX7-FOX01 fusion protein avoids degradation by remaining in the nucleus.19
Positive expression of PAX7 indicates poor prognosis of pediatric and adolescent AML patients
Published in Expert Review of Hematology, 2020
Tianyou Yan, Duolan Naren, Yuping Gong
PAX7 is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. Furthermore, PAX7 was well studied in postnatal skeletal muscle development. In mouse skeletal muscles, PAX7 was expressed in proliferating myoblasts and was downregulated after myogenic differentiation [10]. Consistently, during differentiation of goat skeletal muscles, PAX7 expression in satellite cells was significantly downregulated [11]. PAX3 and PAX7 are co-expressed in the dermomyotome during mouse embryonic development [12]. Their expression gives rise to myogenic progenitor cells, which are necessary for myogenic development. Unlike its partner, PAX7 is predominantly required for adult myogenesis and specifies the adult stem cell population in muscles [10,13,14]. Moreover, the expression of PAX genes is also essential for growth and survival of certain cancers [15–17]. Studies showed that PAX5 expression occurs in various types of malignant tumors, including hematological malignancies, B-cell non-Hodgkin lymphoma, and Hodgkin lymphoma [17]. However, PAX7 expression is a unique feature of rhabdomyosarcoma and Ewing sarcoma [18]. In fact, PAX7 expression was present in 86% of rhabdomyosarcoma cases, and its expression was significantly increased in Ewing sarcoma compared to other soft tissue tumors, demonstrating the utility of immunohistochemical analysis of PAX7 expression as a diagnostic marker of Ewing sarcoma and rhabdomyosarcoma [18,19].
Ectopic CD137 expression by rhabdomyosarcoma provides selection advantages but allows immunotherapeutic targeting
Published in OncoImmunology, 2021
Kang Yi Lee, Hiu Yi Wong, Qun Zeng, Jia Le Lin, Man Si Cheng, Chik Hong Kuick, Kenneth Tou En Chang, Amos Hong Pheng Loh, Herbert Schwarz
Another interesting correlation is that the frequency of Ras gene mutations correlates with the absence of Pax gene fusions, i.e., Ras mutations are completely absent in fusion-positive ARMS.47 Since oncogenic K-ras has been shown to promote CD137 expression in pancreatic cancer, mutated Ras may contribute to the higher prevalence of CD137+ cases in ERMS, PRMS and SC-RMS.48 Although hypoxia has been shown to induce CD137 in malignant cells, we could not confirm that for RMS cell lines.49