Acute Leukamia Pre-Lecture Material

• Mutations can be divided into three main types, including:

  • chromosome mutations,
  • genome mutations,
  • single-gene mutations.
• Chromosome mutation refers to any changes in chromosome structure
• Genome mutation refers to any changes in chromosome number
• Single-gene mutation refers to relatively small changes in DNA structure that occur within a particular gene
• The changes of nucleotide sequences could result in amino acid sequences alternation, causing abnormal protein production.
• Epigenetics refers to the alteration of gene expression with wild-type DNA sequences being maintained via the process of hypermethylation (addition of a methyl group) or hypomethylation (removal of a methyl group)
• The total amount of genetic information in the chromosome can be changed due to deficiencies/deletions or duplications
• Deletion refers to the loss of a chromosomal segment
• Duplication refers to the repetition of a chromosomal segment compared to the normal parent chromosome
• The genetic material in the chromosome could remain the same but is rearranged due to inversions or translocations
• Inversions refer to a change in the direction of part of the genetic material along a single chromosome
• Translocations refer to a segment of one chromosome that becomes attached to a different chromosome
• Chromosome numbers can vary in two main ways, euploidy, and aneuploidy - Euploidy refers to variation in the number of complete sets of chromosomes while aneuploidy refers to variation in the number of particular chromosomes within a set.
• The single-gene mutation is commonly known as a point mutation, in which alternation of a single nucleotide in a gene sequence is usually observed.  Point mutation could be caused by base substitution, deletion, or insertion.
• There are two types of base substitution, transition and transversion. Transition refers to a change of a pyrimidine (C, T)  to another pyrimidine or a purine (A, G) to another purine. Transversion refers to a change of pyrimidine to purine or vice versa.
• Deletion refers to a single nucleotide that is deleted from the DNA while insertion refers to a single nucleotide is inserted into the DNA.
• Point mutation alters the coding sequence - however, the amino acid sequence might not be necessarily changed as point mutation could cause silent mutation, missense mutation, nonsense mutation, and frameshift mutation.
• The base substitution that does not alter the amino acid sequence of the polypeptide is known as silent mutation.
• The base substitution which cause an amino acid change is known as a missense mutation. 
• The base substitution that changes a normal codon to a termination codon is known as a nonsense mutation.
• A Frameshift mutation is caused by the addition or deletion of nucleotides in multiples of one or two
• apoptosis is a normal cellular process causing programmed cell death and involves three main pathways:

  1. extrinsic
  2. intrinsic
  3. perforin/granzyme
• The extrinsic pathway is in response to external cell signals binding to death receptor - Caspases activate cytoplasmic endonucleases to cause the degradation of nuclear and cytoplasmic material
• the intrinsic pathway is dependent on mitochondrial signalling - Cytochrome C activates caspases which cause an activation of the execution pathway. this is controlled by tumour suppressors, such as p53
• the perforin/granzyme pathways is mediated by cytotoxic T lymphocytes - Antigen presenting cells activate cytotoxic T lymphocytes to find infected cells and trigger caspases which cause DNA fragmentation which leads to apoptosis