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Related Concept Videos

Mutations01:39

Mutations

94.5K
Overview
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Mutations01:35

Mutations

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Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
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Viral Mutations00:36

Viral Mutations

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Mutation, Gene Flow, and Genetic Drift01:09

Mutation, Gene Flow, and Genetic Drift

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In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
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Mutations in Microorganisms01:18

Mutations in Microorganisms

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Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
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Point and Frameshift Mutations01:30

Point and Frameshift Mutations

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Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
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Related Experiment Video

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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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Patterns of mutations in TP53 mutated AML.

John S Welch1

  • 1Department of Internal Medicine, Washington University, 660 Euclid Ave, Box 8007, St. Louis, MO 63110, USA.

Best Practice & Research. Clinical Haematology
|November 24, 2018
PubMed
Summary
This summary is machine-generated.

TP53 mutated acute myeloid leukemia (AML) shows poor response to chemotherapy. Decitabine offers an alternative treatment, but further consolidation may be needed for better outcomes in TP53 AML patients.

Keywords:
AMLAcute myeloid leukemiaCHIPClonal hematopoiesis of indeterminate potentialDecitabineMDSMutation patternsMyelodysplastic syndromesTP53

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • TP53 mutations in acute myeloid leukemia (AML) are associated with poor prognosis and limited treatment options.
  • Standard chemotherapy yields suboptimal outcomes for patients with TP53-mutated AML.
  • Despite challenges, TP53 mutations should not preclude treatment initiation.

Purpose of the Study:

  • To review the clinical and genomic characteristics of TP53-mutated AML.
  • To discuss current and emerging treatment strategies for TP53-mutated AML.
  • To highlight Decitabine as a potential therapeutic option.

Main Methods:

  • Literature review of clinical studies and genomic analyses.
  • Analysis of treatment outcomes in TP53-mutated AML cohorts.
  • Examination of Decitabine's efficacy and limitations in TP53-mutated AML.

Main Results:

  • TP53-mutated AML exhibits resistance to conventional chemotherapy, leading to short overall survival (median 5-9 months).
  • Decitabine shows promise as an alternative treatment for TP53-mutated AML.
  • Decitabine's efficacy may be limited by a lack of deep molecular remissions, necessitating consolidation therapy.

Conclusions:

  • TP53-mutated AML remains a challenging clinical entity with poor therapeutic response.
  • Decitabine represents a viable alternative, though its role requires further investigation and optimization.
  • Comprehensive understanding of TP53-mutated AML's characteristics is crucial for developing effective treatment paradigms.