Cytogenetic Analysis - Cytogenetics

Cytogenetics is a field of study that deals with chromosomes and related abnormalities. Chromosome analysis is also known as karyotyping and involves the pairing of homologous chromosomes.

Abnormalities in chromosomes cause several genetic disorders leading to developmental delay, congenital malformations, mental retardation, and infertility. Cytogenetic analysis is very crucial in the diagnosis of oncologic and hematologic disorders.

It helps in the diagnosis and classification of disease as well as in planning treatment regimens and monitoring the status of disease.

Researcher holding cytogenetic pictures of chromosomes - Image Copyright: RHIMAGE / Shutterstock
Researcher holding cytogenetic pictures of chromosomes - Image Copyright: RHIMAGE / Shutterstock

Cytogenetic Analysis in AML

Cytogenetic analysis plays a critical role in the diagnosis, classification, prognosis, and management of acute myeloid leukemia (AML). It has become an essential technique that helps doctors identify leukemia and provide treatment guidance. Cytogenetic testing is usually performed on the bone marrow of AML patients and helps in characterizing the aggressiveness of leukemia. Moreover, it assists in determining treatment response and overall prognosis.

Genetic analysis of FLT3, CEBPA, and NPM1 mutations is now standard practice in case of AML patients. AML risk factors are determined by identifying the underlying cytogenetic abnormalities, including chromosomal duplications, deletions, or substitutions and also under- or over-expression of some proteins.

A translocation involving chromosomes 15 and 17 referred to as t(15;17) is linked to acute promyelocytic leukemia (APL), which is a distinct AML subtype. Cytogenetic abnormalities are associated with 3 categories of disease - better-risk (65% long-term survival), medium-risk (25% long-term survival), and poor-risk (<10% long-term survival) disease.

Molecular markers also play a key role in AML prognosis. FLT3 gene mutations are very common in AML and are seen in as much as one third of AML patients. FLT3 internal tandem duplications are present in 25% of AML cases and are associated with poor prognosis. NPM1 mutations are associated with intermediate or better risk and are usually favorable with patients responding well to chemotherapy.  But NPM1 present along with FLT3 mutation is unfavorable. Mutations in CEBPA gene are associated with normal cytogenetic findings, longer remission, and improved overall survival.

Cytogenetic Testing Methods

Karyotyping or Routine Cytogenetic Analysis

This helps detect structural or numerical chromosome abnormalities. Chromosome analyses require cell cultures and involves the harvesting of chromosomes, chromosome banding, microscopic analysis and the production of karyotypes.

Molecular Cytogenetic Testing (FISH)

It is also called fluorescence in-situ hybridization (FISH). FISH testing involves the determination of the presence, absence, position, and copy number of DNA segments with the help of fluorescence microscopy.

  • Metaphase FISH (Microdeletion FISH) - Metaphase FISH studies help in detecting changes such as microduplications and microdeletions in phenotypic findings.
  • Dual-Color / Fusion FISH - This study is used to detect neoplastic rearrangements that affect two specific loci, but cannot detect variant, complex, and/or atypical rearrangements of the same loci.
  • Dual-Color/Break-Apart FISH - This technique uses DNA probe systems to identify specific loci that cause rearrangements in several translocation partners.
  • Interphase FISH - Interphase FISH studies provide information regarding enumeration or rearrangement in specific DNA probes, but other structural inferences are not possible using this technique.

Microarray Comparative Genomic Hybridization (aCGH) Testing

This kind of testing helps detect genomic copy number changes or minor genetic imbalances, such as gain or loss of chromosomal material, which cannot be detected by traditional FISH or cytogenetic analysis methods. It also helps to identify specific genes involved in a chromosomal abnormality that was detected using conventional FISH or cytogenetic testing methods.


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