Chronic myeloid leukemia (CML) is a rare blood cancer that develops in the bone marrow. Karyotyping is a genetic technique doctors use to diagnose CML and choose more effective treatments.

Karyotyping involves examining a person’s chromosomes, which allows a doctor to determine CML alongside the best course of treatment. The procedure also influences an individual’s outlook.

This article explains the role of karyotypes in the diagnosis and management of this type of blood cancer.

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Each human cell contains 23 sets of chromosomes, which carry genetic information needed for growth and survival.

A karyotype is the number and physical appearance of all chromosomes in a person’s body. Scientists define karyotyping as the process of pairing and ordering all the chromosomes of an organism.

In the last few years, karyotypes have increasingly become a source of diagnostic information. They may help predict birth defects, genetic disorders, and some cancers, including CML.

A karyotype analysis can reveal structural changes of chromosomes, such as:

  • deletions
  • duplications
  • translocations
  • inversions

In most cases, cells correct these mistakes, and there is no adverse impact. But sometimes, the changes go unchecked or uncorrected, which results in uncontrolled cell growth or cancer.

According to the American Cancer Society, DNA changes related to CML develop during a person’s lifetime. They do not inherit them from a parent.

To better understand normal and complex karyotype CML, it helps to discuss the Philadelphia (Ph) chromosome.

In most people, CML develops at the stage of cell division. At this stage, DNA is swapped or ‘translocated’ between chromosomes 9 and 22. Simply put, a part of chromosome 9 goes to 22, and part of chromosome 22 goes to 9.

This translocation leads to the formation of a new abnormal chromosome called the Philadelphia (Ph) chromosome. This new chromosome 22 appears shorter in people with CML.

The DNA swap between chromosomes leads to the formation of a new fusion gene called BCR-ABL. This gene goes on to produce the BCR-ABL protein, which causes CML cells to grow out of control.

Doctors consider the Ph translocation an important biomarker to predict and track a person’s progress with chronic myeloid leukemia.

Research shows that close to 90% of people with CML have the Ph chromosome at diagnosis. Others, however, have normal or complex karyotype CML.

In people with normal karyotype CML, the chromosomes appear normal in shape, size, and structure. That is, all 23 pairs of chromosomes look just like healthy chromosomes found in people without CML.

According to a 2020 study published in the journal Nature, 5%–10% of people with CML have a normal karyotype at the time of diagnosis.

They do not show the presence of the Ph chromosome — or any other chromosomal abnormalities — during karyotype analysis.

Interestingly, despite having a seemingly normal karyotype, people with CML still have the BCR–ABL gene. Tests such as the fluorescence in situ hybridization (FISH) or reverse transcription-polymerase chain reaction (RT-PCR) help detect this gene promptly.

Scientists define a complex karyotype as the presence of three or more chromosomal abnormalities, with at least one being a structural abnormality.

About 5% of people with CML have other types of translocations.

Researchers have identified two subgroups of variant translocations: simple and complex variants. They differ based on the results of molecular biology and R- and G-banding, which are types of dye-staining techniques.

The remaining set of people with CML may have additional changes in their chromosome makeup. This is called clonal evolution (CE).

Studies show that this last group of individuals experience more treatment complications and poorer outcomes from their cancer therapy.

Unlike FISH and RT-PCR tests, karyotypic analysis makes it possible to detect chromosomal changes other than the standard 9,22 Philadelphia translocation.

Karyotyping has proven useful in detecting major and minor route additional chromosomal abnormalities (ACAs), as well as variant translocations.

Finding these detections helps doctors determine the best course of treatment and overall disease outlook.

To effectively treat CML, doctors use a combination of treatments, including:

Before starting treatment, the doctor checks the person’s karyotype to understand the type of CML and the chromosome changes present at the genetic level.

They begin by collecting cells taken from a blood or tissue sample.

Under laboratory-controlled conditions, they stimulate these cells to begin dividing.

This is followed by abruptly arresting chromosome division (in metaphase), preserving in a fixative, and then applying the sample to a slide.

A colored dye then stains the sample to help visualize the distinct banding patterns of each chromosome pair.

Any abnormal appearance in chromosome shape, length, or structure becomes apparent on the stained slide. They record these changes and compare them to a normal karyotype, which helps confirm a diagnosis of CML.

A person’s karyotype influences the choice of treatment and outlook with CML.

For instance, most people with the Ph chromosome respond well to tyrosine kinase inhibitors (TKIs), a class of drugs that targets the BCR-ABL fusion gene.

This therapy has considerably changed the clinical landscape of CML for the better, turning it from a life threatening disease into a manageable, chronic condition.

Some people with CML have additional chromosomal abnormalities (ACAs) in Ph+ cells. These classify into “major” and “minor” route changes.

In these cases, the abnormalities result in poorer treatment outcomes. ACAs interfere with disease progression and increase in the advanced stage, from 30% in the accelerated phase to 80% in the blastic phase of CML.

The National Comprehensive Cancer Network (NCCN) recommends karyotyping at 3 and 6 months after starting TKI therapy to monitor progress.

Chronic myeloid leukemia is a rare but treatable blood cancer. A genetic technique called karyotyping helps doctors understand the genetic cause of the disease and choose suitable treatments with better clinical outcomes.

A karyotype analysis can also predict the impact and progress of CML. Therefore, experts recommend this test at diagnosis and regular intervals during the person’s treatment journey.