Precision medicine in acute myeloid leukemia
Debmalya Barh in Precision Medicine in Cancers and Non-Communicable Diseases, 2018
A new provisional entity AML with mutated RUNX1 (excluding cases with myelodysplasia-related changes) was added (Gadzik et al., 2016; Haferlach et al., 2016). Myeloid neoplasms with germ line predisposition is also a new category that was added to the WHO classification (Babushok et al., 2016; Churpek and Godley, 2016; Table 10.4). The molecular basis of AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) was revisited showing that repositioning of a GATA2 enhancer element leads to overexpression of the MECOM (EVI1) gene and to haploinsufficiency of GATA2 (Gröschel et al., 2014).
Animal Models and Imaging of Intervertebral Disc Degeneration
Raquel M. Gonçalves, Mário Adolfo Barbosa in Gene and Cell Delivery for Intervertebral Disc Degeneration, 2018
Many other genetic models have been described with DDD, including, for example, Cmd aggrecan knockout mice (Watanabe and Yamada 2002), progressive ankylosis mice (Sweet and Green 1981), a Mecom mutation in mice (Juneja et al. 2014), caveolin-1-null mice (Bach et al. 2016), neurofibromatosis type 1 mice (Rhodes et al. 2015; Wang et al. 2011), murine progeroid syndrome (Vo et al. 2012), and HLA-B27 rats (Hammer et al. 1990; Taurog et al. 1993).
MECOM gene overexpression in pediatric patients with acute myeloid leukemia
Published in Acta Oncologica, 2022
Mariam Elsherif, Mahmoud Hammad, Hanafy Hafez, Dina Yassin, Mohamed Ashraf, Nouran Yasser, Leslie Lehmann, Alaa Elhaddad
MECOM gene overexpression reportedly occurs in approximately 8–15% of pediatric patients with AML and has been associated with an adverse prognosis in both adult and pediatric myeloproliferative neoplasms [6–8]. Therefore, assessment of MECOM gene expression, in addition to other known molecular and cytogenetic abnormalities, could provide a wider biological landscape and further clinical information that will help in the application of a better risk stratified therapy, especially in patients with AML that lack other known genetic abnormalities [9]. Previous studies of MECOM expression in pediatric AML from European cooperative groups and from the Children Oncology Group (COG) study AAML03P1 reported that its overexpression adversely impacted event-free survival (EFS) and overall survival (OS) in univariate analyses, but not in multivariate analyses [8,10].
A family case series of inherited thrombocytopenia
Published in Baylor University Medical Center Proceedings, 2023
Artur Borkowski, Jakub Gawryś, Gracjan Iwanek, Jarosław Dybko
In the conducted study, molecular assessment targeted genes related to predisposing forms of IT. In certain forms of IT, thrombocytopenia present at birth or in early childhood can evolve to bone marrow aplasia and pancytopenia.10 Since some probands presented low platelet count in infancy, molecular and cytogenetic analysis included mutations of MPL and MECOM, causative genes of congenital amegakaryocytic thrombocytopenia (CAMT) and MECOM-associated syndrome (MECOM-AS), respectively.10 While CAMT is an autosomal recessive disease, MECOM-AS presents an autosomal dominant inheritance pattern.10 Familial platelet disorder with propensity to acute myelogenous leukemia, caused by RUNX1 mutations, and ETV6-related thrombocytopenia have an autosomal dominant inheritance pattern and clinically present as mild to moderate thrombocytopenia with normal platelet size and morphology, what was reported in several probands in this study.2GATA1 mutations are found in almost all cases of transient myeloproliferative disorder and acute megakaryoblastic leukemia in children with DS, typically involving exon 2.11,12 Nearly 30% of newborns with DS are born with a GATA1 mutation.5 Since the prevalence of ITs predisposing to other diseases ranges from 45% to 50% of known forms of ITs, a complete blood count and peripheral blood smear examination once a year should be offered.2 According to Makris, a 3-week therapeutic trial of eltrombopag after diagnosis of IT is suggested to determine response to thrombopoietin receptor agonists.13
Related Knowledge Centers
- Activin & Inhibin
- Bone Morphogenetic Protein
- Protein
- Retrovirus
- Transforming Growth Factor Beta
- Myelodysplastic Syndrome
- Gene
- Acute Myeloid Leukemia
- Chronic Myelogenous Leukemia
- Activin & Inhibin
- R-Smad