Whether it is a family member, friend, or colleague, most of us know an individual that has been diagnosed with cancer. A publication from the American Cancer Society claims that one in two males and one in three females will develop cancer during their lives (Howlader 2016). When considering the social networks of those diagnosed with cancer, nearly everyone is impacted by cancer in some shape or form. Despite the extensive amount of money and research invested into curing cancer, the Center for Disease Control and Prevention reports that cancer is the second leading cause of death in the United States – accountable for 599,108 deaths in 2017 (Heron 2018). To put that into perspective, cancer took 20,000 more lives in 2017 than the population of Wyoming in 2018 (US Census Bureau 2018).
One of the most important questions asked after a cancer diagnosis is: What is my prognosis? Or, what are the chances that I survive this cancer? While each case of cancer is unique, scientists are working to better characterize specific types of cancer. Often times, a single mutation can have cascading effects on the function of processes within the body. A recent study suggests that a mutation in the TP53 tumor suppressor gene has a strong negative correlation with the survivability of cancer patients with Acute Myeloid Leukemia (Hou 2015).
Acute Myeloid Leukemia (AML) is a type of cancer that tends to start in the bone marrow and spread to other parts of the body such as the lymph nodes, liver, spleen, central nervous system, and testicles. In most cases, the cancer develops from cells that were to be white blood cells (ACS 2018). According to the American Cancer Society, AML makes up 33% of adult leukemia diagnoses with a predicted number of 19,940 new cases of acute myeloid leukemia this year (NCI 2020). Understanding the relationship between the TP53 gene mutation and cancer survivability could provide a more conclusive answer for our loved ones diagnosed with AML.
The TP53 tumor suppressor gene is one of the most frequent alterations in cancer (Hou 2015). The TP53 gene codes for a protein that serves as the “guardian of the genome.” The protein regulates cell division and prevents tumor formation, signaling for the cell to commit apoptosis – or cell death – if the genetic damage is irreparable (USNHLM 2020). The effects of the mutation in the gene, however, are vaguely understood – leading to questions such as, “How does this mutation interact with other genetic alterations in AML?” and, “How stable is the mutation throughout the progression of the disease/treatment?”
A recent study by Dr. Hsin-An Hou’s work stems from studies in the field that prove contradictory or inconclusive. Previous studies demonstrate that TP53 mutations are frequently detected in patients with therapy-related AML or AML with complex karyotype (CK). One British study reported that the incidences of the mutation in AML-CK were 53%, while two German studies reported 60-69% (Hou 2019). There are discrepancies regarding the use of the TP53 mutation as a prognosis factor as Rutger et al. concluded that the mutation was an independent factor for overall survival; although, Bowen et al. did not conclude the same. Identifying the inconsistencies in the field, Dr. Hou and his team delved into these unknowns to better understand the implications of the TP53 mutation.
Working under the National Taiwan University Hospital, Dr. Hou and his team explored these questions and incomplete understandings by studying 500 AML patients – 35 of which have TP53 mutations – in Taipei, Taiwan. After conducting the research between the years of 1995 and 2008, this study was published in the Blood Cancer Journal in 2015.
To qualify for the study, the patients must have been newly diagnosed with AML and could have no previous medical history of hematological or therapy-related AML. Analysis of the TP53 gene was performed in two ways. First, the patient samples were exposed to a panel of substances (monoclonal antibodies) that enabled the characterization of the cells based on their reaction with the panel. Dividing the samples into groups based on the antibodies allowed the researchers to evaluate their research question: How does this mutation [TP53] interact with other genetic mutations? Second, the researchers sequenced 420 samples of DNA from 113 patients directly after or within one to three days of bone marrow harvesting. Sequencing the DNA provided insight on which patients experienced the TP53 mutation and where the mutation occurred in the DNA.
Dr. Hou’s research results are monumental in the growing field of cancer immunotherapy. The study highlights the importance of the TP53 gene mutation as it is a strong indicator of patient survival. In the study, the patients with the gene mutation displayed an overall survival of five months. The patients without the mutation, however, presented an overall survival rate of thirty-five months – living on average seven times the longer than patients with the mutation. Additionally, the study presents that the TP53 gene mutation remains present throughout the progress of cancer, and patients with the TP53 gene mutation display lower incidences of other mutations.
The authors note that the relatively small sample size of patients with the TP53 mutation and variation in the treatments of the patients could be potential sources of error. Although, it appears that the limits of the study parallel the limits of cancer research as a whole. Due to the fact that medical professions are morally obligated to give their patients the best possible treatment, there was variation in the treatment of the patients in the study. The dosage and drugs used for chemotherapy were adapted to the needs of the patient. Also, the specific criteria of the study limited the pool of patients that qualified for the research. A study in a larger hospital or group of hospitals could be performed to obtain a more robust sample size.
Awareness of the relationship between the TP53 mutation and patient survivability is meaningful to all types of individuals. For medical professionals, this discovery serves as the basis for future research. Dr. Paul Armistead and his lab at UNC-Chapel Hill are currently investigating the reason for this negative correlation. For patients and loved ones, this research makes cancer less ominous. Being able to better understand what the future holds can be reassuring for many patients. This information could also serve as a testament for the extensive research that has been invested in understanding cancer – proving that treatment for cancer extends past a single doctor and a single patient.
When confronted with the gravity of a cancer diagnosis, it is important to maintain hope. Researchers across the globe dedicate their lives to saving your family member, friend or colleague from cancer. While the current prognostic an AML patient with a TP53 mutation may be poor, progress is made each and every day.
References
[ACS] The American Cancer Society medical and editorial content team. 2018. What is Acute Myeloid Leukemia (AML)? American Cancer Society.Heron M. 2018. Death: leading causes 2017. National Vital Statistics Reports. Center for Disease Control and Prevention. Volume 68: Number 6.
Hou, H. A., Chou, W. C., Kuo, Y. Y., Liu, C. Y., Lin, L. I., Tseng, M. H., et al. 2015. TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution. Blood cancer journal, 5(7), e331. doi:10.1038/bcj.2015.59.
Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). 2016. SEER Cancer Statistics Review, National Cancer Institute.
[NCI] National Cancer Institute. 2018. SEER cancer stat facts: Acute Myeloid Leukemia. American Cancer Society.US Census Bureau. 2019. Wyoming population estimate. US Department of Commerce.
[USNLM] U.S. National Library of Medicine. 2020. TP53 gene. Genetics Home Reference. https://ghr.nlm.nih.gov/gene/TP53#.