Introduction
Acute Myeloid Leukemia, often known as AML, is a specific kind of cancer that starts in the bone marrow, the soft interior part of the bone where new blood cells are produced. Acute means this type of cancer manifests fast and worsens rapidly if left untreated. Myeloid refers to the abnormal type of white blood cells that accumulate in the bone marrow for ALM.
Leukemia is a type of cancer that begins in blood-forming cells in the bone marrow. These cancer cells frequently leak into the bloodstream and circulate throughout the body. ALM is the most common type of acute leukemia in adults and needs to be tested and detected early for treatment to be effective. So, from a prognostic point of view, it is essential to understand the molecular features of the disease better to predict its behavior and share the prognosis with the patient.
Genetic Tests for AML
FISH Test
FISH is an abbreviation for Fluorescence in SITU Hybridization, a technique that detects gene alterations in cells. The cell may create too much or too little protein if a gene changes. The gene changes can cause cancer cells to grow and replicate faster than usual.
A pathologist performs the FISH test, which requires a sample of bone marrow, blood, or cancer tissue. The pathologist uses a dye and ultraviolet light in the laboratory to detect and count gene alterations. Significant alterations are the identification of AML. The fluorescent probes to identify DNA sequences are the most common technology for detecting AML because of their greater stability, safety, and ease of detection.
Molecular Testing
PCR Test
Polymerase chain reaction (PCR) is a sensitive technique for detecting genetic mutations and chromosomal alterations that are too tiny to observe under a microscope. It involves collecting bone marrow or blood from the patient. The test method comprises tagging the PCR genes with fluorescent dyes or staining the amplified DNA product with a chemical dye.
The test amplifies specific DNA or RNA (ribonucleic acid) fragments to make them easier to detect and quantify. It can detect leftover cancer cells in the body following treatment. Technologies that support PCR testing include thermal cyclers, gradient PCR equipment, and qPCR equipment.
DNA Sequencing
The process of determining the relative positions of the four fundamental components that make up a DNA molecule is known as DNA sequencing. A sequencer machine produces chemical synthesis, but computer software analyzes sequences to generate test results. The sequence informs scientists about the genetic information a particular DNA segment carries. Furthermore, sequence data can indicate alterations in a gene that may cause disease—identifying these genetic alterations aids in diagnosing the specific subtype of AML and selecting treatment choices.
The next-generation sequencing (NGS) method is revolutionary. It offers a very efficient, scalable, and quick approach to massively parallel DNA sequencing. Nevertheless, DNA sequencing is more technically challenging and costly to use. Examples of NGS technologies released in the last decade that enable enormous parallel sequencing include Illumina MySeq, HiSeq, the SOLiD system, and Ion Proton.
Karyotype Genetic Test
Acute Myeloid Leukemia can be diagnosed using a Karyotype test, which looks at the number, size, and shape of chromosomes in a blood or bone marrow cell sample. Chromosomes are thread-like structures that contain the genetic blueprint for the body. Chromosome imbalances can cause serious problems with growth, development, and health.
This test requires a blood sample from an arm vein, bone marrow, or tissue sample. For the bone marrow aspiration, your healthcare provider will inject a needle into the bone and draw a sample of bone marrow fluid. Extracting bone marrow samples is quick and has no health consequences except minor bruises caused by the needle.
A karyotyping test increases the number and structure of a person’s chromosomes to find anomalies. A specialist examines the size, shape, and quantity of chromosomes in the blood or bone marrow cell sample using a microscope. The stained piece is photographed to illustrate the chromosomal configurations. The amount of chromosome abnormalities detected by a karyotype test reflects the severity of AML. GTG-banding, Fluorescent in situ hybridization (FISH), Spectral karyotyping, and Comparative genomic hybridization are the techniques most frequently utilized for routine karyotype characterization (CGH).
Prevalence of AML in the US and the Most Vulnerable Population
The most prevalent kind of leukemia in adults is AML. However, AML is generally uncommon, making up only approximately 1% of all tumors (American Cancer Society, 2019). About 4.2 new cases per 100,000 people each year affect men and women. Each year, there are over 20,000 new cases of AML in the United States (American Cancer Society, 2019). Whites who are non-Hispanic are more likely to be diagnosed with ACM than any other ethnicity, as indicated by the American Cancer Society (2019).
With a ratio of 5:3, males predominate over females. Recent enhancements to management guidelines have increased cure rates by 15% for patients over 60 and by 40% for those under 60. Although the average life expectancy has marginally increased, the average patient’s longevity has significantly decreased (Vakiti & Mewawalla, 2019). Therefore, reasonable information about survival should be provided to patients.
Despite improvements in treatment methods, the outlook for the older population is still terrible. Acute myeloid leukemia was expected to affect 69,700 persons in the US in 2019, according to the National Cancer Institute (2018). Data from 2017 to 2019 show a 0.5% prospect of both genders getting diagnosed with AML at some time in their lives (National Cancer Institute, 2018). These figures show that AML is becoming increasingly common among adults, emphasizing the necessity for frequent and sophisticated testing.
AML often affects elderly patients and is rare in persons under 45. People with AML are typically 68 or older when they receive their initial diagnosis (Vakiti & Mewawalla, 2019). However, AML can also affect youngsters. AML is more prevalent in men than women, but both sexes have an average lifetime risk of AML of roughly 1% (American Cancer Society, 2019). Some AML patients may respond very well to treatment, but not everyone does, and side effects are frequently severe or even fatal. Studies are being conducted to develop safer and more efficient therapy for AML.
Mutations in AML
Mutation in AML of DNA Methylation
One mutation common in AML is the DNMT3A, which leads to a decrease in normal enzyme function. According to Park et al. (2020), 20% of AML cases have DNMT3A mutations, which are reported to reduce the DNA methylation activity. In the cell, many methods exist for controlling how DNA is read and expressed. Several of these methods, called epigenetic modifications, can turn specific genes on or off without altering the DNA sequence.
One of these methods is DNA methylation, which happens when a methyl group is introduced to a DNA base. When this happens, additional protein can no longer bind to the region of the DNA. It stops the DNA from being copied into RNA, which is a messenger that carries DNA instructions. Consequently, the gene is turned off. Normal DNA methylation is vital for the development of healthy cells.
In cancer cells, abnormal DNA methylation patterns are seen. Genes that would usually suppress tumor growth see higher levels of methylation and are turned off. At the same time, genes that increase tumor growth, called oncogenic, see a decrease in methylation and are turned on. This results in unregulated tumor growth.
Tumor Suppressor Gene Mutation
The TP53, also called the p53 gene, is one example of a tumor suppressor gene associated with low survival outcomes in AML. Despite being the most mutated gene in cancer, it is found in only 5-10% of patients who have not been exposed to AML therapies or agents and in 30% of patients with therapy-related AML (George et al., 2021).
The special protein called p53 is recruited rapidly in response to DNA damage. It finds damaged sites on a DNA repair or destroys it if it is badly damaged. If the p53 is damaged, the protein cannot bind to DNA securely. This means that no decision can be made on whether to repair the DNA or destroy the cell. Cells can accumulate more damaged DNA over time, which is likely to grow out of control, leading to the formation of tumors.
Conclusion
Acute myeloid leukemia is a type of cancer that starts in the bone marrow and spreads into the blood. Advanced techniques for testing AML include fluorescence in situ hybridization, polymerase chain reaction, DNA sequencing, and Karyotype genetic tests. These tests require extracting blood, bone marrow, or tissue samples from the patient.
People mostly affected by AML are adults aged over 45, but it can affect people of all ages. AML affects over 20,000 people in the United States each year, with most patients being over the age of 60. Overall, genetic testing is more necessary now than ever because of mutations that require extensive analysis of the molecular structure of cancer-causing cells.
References
American Cancer Society. (2019). Key Statistics for Acute Myeloid Leukemia (AML). Cancer Organization: American Cancer Society. Web.
George, B., Kantarjian, H., Baran, N., Krocker, J. D., & Rios, A. (2021). TP53 in Acute Myeloid Leukemia: Molecular Aspects and Patterns of Mutation. International Journal of Molecular Sciences, 22(19), 10782. Web.
National Cancer Institute. (2018). Acute Myeloid Leukemia – Cancer Stat Facts. SEER. Web.
Park, D. J., Kwon, A., Cho, B.-S., Kim, H.-J., Hwang, K.-A., Kim, M., & Kim, Y. (2020). Characteristics of DNMT3A mutations in acute myeloid leukemia. Blood Research, 55(1), 17–26. Web.
Vakiti, A., & Mewawalla, P. (2019). Cancer, Acute Myeloid Leukemia (AML, Erythroid Leukemia, Myelodysplasia-Related Leukemia, BCR-ABL Chronic Leukemia). NIH Government; StatPearls Publishing. Web.