China
Africa
Explore chapters and articles related to this topic
Pediatric Oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Stephen Lowis, Rachel Cox, John Moppett, Helen Rees
Genetic analysis is similarly of critical importance, as recurrent genetic alterations play a key part in defining risk groups in childhood AML. A combination of karyotyping, FISH, and RT-PCR is used to identify the common recurrent translocations seen in AML, namely t(8;21), inv(16), t(15;17), and KMT2A rearrangements. It is increasingly clear that identifying the partner gene in KMT2A rearrangements is important as these have significant prognostic impact. Alterations in FLT3 and NPM1 and an increasing list of rare genetic abnormalities of prognostic impact are increasingly screened for in international trials.
Paediatric oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Stephen Lowis, Rachel Cox, John Moppett, Antony Ng
Genetic analysis is similarly of critical importance, as recurrent genetic alterations play a key part in defining risk groups in childhood AML. A combination of karyotyping, FISH and RT-PCR are used to identify the common recurrent translocations seen in AML, namely, t(8;21), inv (16), t(15;17) and MLL rearrangements. It is increasingly clear that identifying the partner gene in MLL rearrangements is important as these have significant prognostic impact.45,46 Alterations in FLT3 and NPM1, commonly seen in adult cytogenetically normal AML, are rare in children but should be identified where possible.
Fluorescence In Situ Hybridization and Polymerase Chain Reaction
Published in Wojciech Gorczyca, Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
AML carrying nucleophosmin (NPM1) mutations displays distinct molecular and clinical–pathological features that led to its inclusion as provisional entity in 2008 WHO classification [155–162]. NPM1 is nucleocytoplasmic shuttling protein mainly localized in the nucleolus that has multiple functions, including interaction with TP53 in controlling cell proliferation and apoptosis and controlling DNA repair and centrosome duplication during mitosis. NPM1 mutations (Figure 7.19) are now recognized as the most common genetic lesion in AML, present in 50%–60% of patients with cytogenetically normal AML. NPM1+ AML usually shows monocytic differentiation and a female preponderance, and lacks CD34 expression. NPM1 mutations are prognostically favorable in the absence of FLT3-ITD [160]. NPM1 mutations also have a favorable prognostic impact in older patients with cytogenetically normal AML, especially those aged ≥70 years.
An overview of the molecular and clinical significance of the angiopoietin system in leukemia
Published in Journal of Receptors and Signal Transduction, 2023
Saeed Zaka Khosravi, Samira Molaei Ramshe, Mehdi Allahbakhshian Farsani, Mohammadreza Moonesi, Faroogh Marofi, Majid Farshdousti Hagh
Some have inspected the Ang-1 level in response to different kinds of therapies. Ecotropic viral integration site-1 (EVI1) is a transcription factor and acts as an oncogene in AML. Ichihara et al. described the increased level of Ang-1 in EVL1-high leukemia cells. An elevated level of Ang-1 in EVL1-high leukemia cells precipitates chemotherapy resistance by causing cell cycle suppression and thus maintaining ELV1-high leukemia cells in the BM niche [61]. Multiple detection methods, different sample sizes, and sample heterogeneity may explain this discrepancy among the mentioned findings. To reduce the heterogeneity of the study population, leukemia patients with specific genetic mutations could be analyzed for their Ang-1 expression level. For instance, one of the most frequent mutations in adult patients with AML is NPM1 mutations. AML cells with NPM1 mutations have been introduced as a source of Ang-1 in BM and have shown an increased level of Ang-1 expression in comparison with not mutated NPM1 cells [51,62].
Experimental drugs in clinical trials for acute myeloid leukemia: innovations, trends, and opportunities
Published in Expert Opinion on Investigational Drugs, 2023
Aleksandra Gołos, Joanna Góra-Tybor, Tadeusz Robak
Homebox A (HOX) is a gene family encoding transcription factors crucial for physiological hematopoiesis [14]. They regulate stem cells’ self-renewal and differentiation into progenitor cells [14,15]. Approximately 30% of acute leukemias emerge with overexpression of the HOX A [16]. Mutations leading to that include rearrangements of histone methyltransferase KMT2A (also known as MLL, mixed-lineage leukemia), KMT2A partial tandem duplication (KMT2A-PTD), and nucleophosmin-1 (NPM1) genes [17,18]. KMT2A mutations are more common in pediatric patients, whereas in adults they occur in about 10% of AML and are associated with poor outcomes [16]. In contrast, NPM1 mutations occur more often (25–30% of all cases) and are classified as a favorable risk [16]. Products of the wild-type genes – KMT2A and products of the mutated genes – KMT2A fusion proteins recruit some proteins from chromatin remodeling complex, such as menin, disruptor of telomeric signaling-1 (DOT1L), and bromodomain and extraterminal domain (BET), binds to the promoters of HOXA genes and activate transcription [19]. However, KMT2A fusion proteins and DOT1L bind to KMT2A target genes inappropriately, resulting in histone methylation activation [19].
Cyclin-dependent kinase (CDK) 9 and 4/6 inhibitors in acute myeloid leukemia (AML): a promising therapeutic approach
Published in Expert Opinion on Investigational Drugs, 2019
Daniel J. Lee, Joshua F. Zeidner
Our understanding of the genomic complexity of AML has evolved over the last several years. The largest genomic classification of AML was recently reported whereby somatic driver mutations were assessed in 1,540 newly diagnosed AML patients who enrolled on three prospective multicenter clinical trials through the German-Austrian AML Study Group. This analysis revealed 11 distinct genomic subgroups with biologic and prognostic significance, highlighting the heterogeneity of AML and the unique attributes of each individual tumor [103]. The most common mutations observed in AML are NPM1 and FLT3 mutations, each seen in approximately 25–30% of patients with substantial overlap. The majority of AML patients have at least one driver mutation that is identifiable through next generation sequencing (NGS), and multiple subclones can emerge throughout treatment that can be intrinsically chemoresistant. Subclassification of AML into distinct genomic subsets will provide a springboard for the development of novel targeted therapies allowing us to move closer to a more personalized therapeutic approach for AML.