The Lion King of Cancer — Acute Lymphoblastic Leukemia
A Journey Inside Cancer’s Child Predator
August 20th, 2019 is a day I’ll never forget.
No, there wasn’t a big global event on that day.
No, I didn’t win some award or anything like that.
But someone did die that day. That someone was the old version of myself.
After experiencing weeks of back pain and staying at the children’s hospital for 48 hrs of tests, I was surrounded by half a dozen doctors who said “Milind, it’s cancer.”
My ❤️ just dropped ⬇️ . From that moment on, I knew my life would NEVER be the same again.
But just like me, so many other kids are forced to grow up so fast after a diagnosis like that.
While cancer is a risk at any age of life, this specific cancer I’m talking about that certainly changed my life along with the lives of many other children is Acute Lymphoblastic Leukemia (ALL).
How does Cancer Form?
First, we gotta start with the basics. I am going to describe this phenomenon of cancer using the storyline of o̶n̶e̶ ̶o̶f̶ the greatest Disney movies of all-time, The Lion King. 🦁 👑
Your classic tale of family, friends, and an identity search for who we truly are. But number one, if you haven’t seen the film, I’m not sure what gigantic rock you might be living under (might be Pride Rock), but first take a look at a trailer of the movie here.
But anyway, back to storytime.
Our cells are constantly dividing in order to keep us alive. In fact, about 55 billion cells in your body have divided in the minute that you’ve read this article. That would take over 1600 years to count to that number. Wowza! 🤯
But when this normal cell division mechanism breaks down, it can cause damaged cells to grow and multiply, thus creating mutations in the cell’s genome. The main types of cancer genes are oncogenes, tumour suppressor genes, and DNA repair genes. This is like how everyone in the Lion King lived in perfect harmony until the “mutated” lion of Scar created a plan to overtake the kingdom and destroy every else in the process.
After about 6 mutations (which can occur from things like cells making too many/too little proteins or making abnormal proteins), a normal cell turns into cancer, of which there are over 100 different types.
Similar to how Scar rallied with the pack of hyenas to outnumber the lions, kill Mufasa, and finally take over as King, these cancer cells essentially ignore the signals to stop dividing or to die off (apoptosis) and continue to overtake the body, with many cancers becoming metastatic by spreading to new areas of the body.
The truly evil aspect of cancer is its ability to continue feeding itself as it destroys the rest of the body. As cancer forms by invading nearby tissue and travelling through the lymphatic system and bloodstream to other parts of the body, it actually causes blood vessels to grow towards them so that they have a constant energy supply to continue growing. Similar to how Scar and the hyenas starved the kingdom of food, they still ensured their dominance over the animal world by forcing the other lionesses to hunt on their behalf while they simply relaxed and had their way.
Once there’s enough momentum and power within the enemy, there’s basically no stopping them. Though as a genetic disease cancer may have started from things like errors in cell division, harmful substances like cigarettes, or through inheritance from parents (as mine did), early detection is really what gives one the best fighting chance before cancer simply says…
A True Child Predator
While I was able to awaken the Simba within me to fend off the evil spirits of my cancer, unfortunately not everyone’s story ends like a Disney movie.
Often there is no match-made-in-heaven outcome where you overcome your major obstacle. Life isn’t built that way.
Similar to the protagonist in The Lion King, Acute Lymphoblastic Leukemia (also known as Acute Lymphocytic Leukemia) is most common in children (ages 2–8) and in males more so than females (at about a 1.86:1 ratio). In fact, in children, it represented nearly 1/3 of all cancer diagnoses (more than any other type of cancer) and accounts for 26.1% of all child cancer-related deaths.
However, leukemia forms much differently compared to other forms of cancer. To begin with, most cancers form solid malignant tumours, but since leukemia is a cancer of the blood, this generally doesn’t occur.
It also begins in the bone marrow, where red blood cells (that circulate oxygen), white blood cells (that protect the body from infection), and platelets (creating blood clots when the body is injured) are all produced.
With ALL, these white blood cells stop developing at an immature stage, and these immature cells begin to grow and multiply to overpower the healthy white blood cells, causing people to be more prone to infection. They also prevent red blood cell production, which causes anemia and fatigue, and even results in bleeding and bruising to occur more likely from destroying many of the healthy platelets too.
These details are why in the leukemia diagnosis, a Complete Blood Count (CBC) is done to check the number of red blood cells and platelets, the number and type of white blood cells, the amount of hemoglobin in the red blood cells (the protein that carries oxygen), and the portion of the sample made up of red blood cells.
If nothing is found there (as was in my case), then a bone marrow test is performed to examine its cells under a microscope and look for signs of cancer. If these leukemic blast cells (immature cells) have increased from their normal range of under 5% to at least 20%, then a leukemia diagnosis will be given.
So, this leaves the question… why? Why does cancer seem to prey on the youngest, purest, liveliest, and most free-spirited part of our population? And probably most importantly, how can we stop this “Scar” that is cancer from taking over our “Simba” population?
A Treasure Hunt with No Map
Unfortunately, there isn’t too much hard evidence out there that explains why childhood leukemia is so much more common than any other type of cancer, at least in terms of things kids can actually control. So it’s really hard to determine a preventative solution to the problem without a true understanding of why the problem is beginning in the first place.
Here are a few risk factors that are theorized to be correlated with a childhood leukemia diagnosis:
Lifestyle-related risk factors
In most adult cancer, lifestyle choices such as tobacco use, diet, body weight, and lack of physical activity can play a major role. However, often these factors take many years to truly influence cancer risk, so they aren’t thought of to influence childhood cancers as much.
Genetic risk factors
Inheritance of specific genes such as having a third (extra) copy of chromosome 21 resulting in Down syndrome can result in a 50x greater likelihood of developing leukemia. Another common disorder is Li-Fraumeni syndrome, a rare inherited condition caused by a change in the TP53 gene (my situation), which results in an increased likelihood of developing several kinds of cancer including leukemia. Inherited immune system problems like Bloom syndrome can not only increase the risk of getting serious infections, but is also tied to increased chances of leukemia. Even having siblings (especially twins) with leukemia is shown to increase these odds as well.
Environmental risk factors
Exposure to radiation especially increases these odds. In fact, it was the first cancer that was associated with atomic bomb radiation exposure in Japan, with a steep incline in case numbers within a mere 5 years of the event. Previous chemotherapy exposure also increases the risk of second cancers developing, with leukemia being among the most common forms.
Uncertain/controversial risk factors
Other studies that have shown early signs in studies to increase risks for leukemia include:
- Mother’s age when the child is born (very young/very old)
- Parents’ smoking history (the more they smoked, the higher the risk)
- Exposure to electromagnetic fields (like living near power lines)
- Minimal exposure to germs (could prevent the immune system from fully developing/strengthening, studies have shown that the risk of childhood leukemia is lower for children in daycares within their first year of life)
Now, even though these hypotheses might have correlations to a leukemia diagnosis, an equally if not more mysterious problem is why it is so much more likely to occur in males than in females.
One interesting study out of Harvard might suggest that a certain mutation on the male X chromosome might lead to this increase in leukemia (and overall cancer) diagnoses in their gender.
2 > 1, That’s No Fun
Since one of the main causes of cancer is damage to the tumour-suppressor genes (which normally halt rapid cell division that triggers cancer), it was predicted that since females, who have two X chromosomes compared to a male’s XY chromosomes, would be less prone to cancer because they have two copies of each tumour suppressor gene.
After different tests, they found that while female cells do only have one X chromosome working at a time, “There are about 800 genes on the X chromosome, and for reasons that are still unclear, about 50 genes on that inactive X chromosome stay on.” explains Professor Andrew Lane.
He also found that of the 6 genes that are more commonly mutated in men than in women which lead to cancer, 5 of them are located within these 50 genes in which women have double the tumour suppressors functioning at all times.
As Lane pointed out:
“This tells us that at the fundamental level of the cell itself, there may be differences simply based on the genetics. It also suggests that cancers thought to be the same in women and men actually develop differently. […] This could have implications for the behaviour of the disease or treatment. To me, the coolest thing about this work is that it opens people’s eyes to the possibilities.”
So just to recap; leukemia is a blood cancer that is much more common in boys rather than girls, and even more common in children compared to adults (one of the only cancers that fit into this category). Though there are a few speculations about how/why this is the case, right now there still isn’t much more proof than simply some clinical tests currently underway.
Now, let’s dive another couple of layers deeper into this. Let’s look at how effective some of the present treatment methods are, and how the future of leukemia treatment in children may be revolutionized moving forward.
Playing Fire with Fire
“The art of war teaches us to rely not on the likelihood of the enemy not coming, but on our readiness to receive him.”
From The Art of War by Sun Tzu, these principles can be applied to the strategies used in cancer treatment. We can not simply put our hands together and pray that cancer won’t grow. 🙏
It is by being prepared to face the battle inside one’s body (along with early detection) that gives us the best possible chance to succeed.
Some types of leukemia (including my own) have specific phases of treatment that each have a specific goal. These phases are:
- Induction
In this first phase, the goal is to kill as many leukemia cells as possible in the blood and bone marrow. It usually lasts for 4–6 weeks and is highly intensive. The body can experience many severe symptoms in this phase due to the swarm of new chemicals/drugs it is absorbing in such large quantities. - Consolidation
This next phase begins once the leukemia is in remission. For some, this can take within a month, while for others, even more intense treatment is required to reach this stage. The goal here is to kill any remaining undetected leukemia cells in the body to reduce the chances of a relapse. There are regular appointments that can last around 6 months. - Maintenance
This final phase lasts around two years, and it includes appointments every couple of weeks for treatment to kill any remaining leukemia cells that may have survived the first two phases. Again, this is done to prevent a relapse, and once a patient reaches this stage, they are usually able to begin returning to their regular lifestyle.
While many leukemia diagnoses follow this pattern of treatment, since the types of cancer along with the patient’s response to it varies on such a wide spectrum, many treatments are given indefinitely on a case-by-case basis.
Depending on the type of leukemia one has, their age and overall, and the stage of leukemia they are in (i.e. whether it has metastasized or not and how much), there are a few main treatment categories, like:
- Chemotherapy: It’s the most commonly known treatment for cancer, where medications are given through IV (into a vein) or through oral pills. These chemicals are designed to hopefully kill leukemia cells, but at worst stop them from further dividing. Treatment usually consists of various cycles, so chemotherapy is often given for a couple of weeks at a time with a period of rest to allow the body to recover before the next cycle.
- Radiation therapy: Though it does not kill cancer cells right away, its goal is to damage their DNA to prevent them from being able to divide and survive. However, since it has many negative effects on the human body at high doses, it is usually considered if chemotherapy doesn’t work well.
Immunotherapy: Rather than attacking the cancer cells that invade and destroy one’s immune system directly, this treatment is used instead to strengthen our defence against leukemia. Treatments like CAR T-cell therapy have recently been emerging in many clinical trials, and though it still may not be mainstream for all leukemia diagnoses, it certainly could be an integral part of the time ahead.
Targeted therapy: So now, rather than necessarily attacking the cancer cells directly or strengthening the immune system, this treatment method focuses essentially on starving the leukemia cells from their blood supply. Since cancer cells cause blood vessels to grow towards them, this method attempts to strip away its simply of nutrients needed to continue growing, which can eventually result first in reduced cell division and eventually the death of these cells. It is also less likely to harm the normal, healthy cells in the body.
Hematopoietic cell transplant (a.k.a. stem cell/bone marrow transplant): This usually occurs in one of the later stages of treatment if current cells in the body aren’t responding as desired. By infusing healthy cells from either yourself (before exposure to treatment) or from a donor back into your bloodstream, these cells can divide and form new cells that the body needs (reb blood cells, white blood cells, platelets). In the case of a donor, this new immune system is able to recognize the foreign cancer cells and kill them off.
A Cure For Childhood Leukemia?
Blood Cancer as a Whole
Similar to how cancers like leukemia can very quickly spread around the body through metastasis, with all the innovation and trials happening globally, the goal of future cancer treatments will also be to essentially “metastasize” their protocols for curing patients around the world.
The first of these treatments involve a combination of multiple methods. In a recent study at the UVA Children’s Hospital, using a combination of both immunotherapy and stem cell transplants proved to be the magic formula in minimizing relapses (the cancer coming back).
Their study included 50 patients of ages 4–30 with acute lymphoblastic leukemia who received CAR T-cell therapy, which in short, stands for “chimeric antigen receptor” and basically changes the properties of a patient’s T-cells (responsible for immune system response/defence) in a lab so that they can bind better to cancer cells and kill them.
However, this therapy is not super effective in patients entering and staying in remission, with about a 60% success rate. However, all 29 patients in the study that only used this therapy ALL relapsed within 2 years. 😬
The alternative here is to implement a transplant of donor stem cells shortly after CAR T-cell therapy. Of the 21 patients who followed this protocol, only 9.5% (2/21) relapsed within the next 24 months. 🥳
Though the sample size here is small, if similar statistics are shown on a broader scale, this treatment for leukemia could save countless millions of lives in the future. As pediatric oncologist Dr. Daniel Lee puts it:
“Most of these kids have a single shot at this life-saving and paradigm-changing therapy called CAR-T-cells. We should do all we can to maximize the chance for a cure, and right now that means a transplant after CAR therapy for most.”
Acute Myeloid Leukemia (AML)
For this aggressive type of blood cancer that affects all ages, advancements in society allowed for CRISPR/Cas9 gene-editing technology to show which gene specifically leads to the development of this type of leukemia. 🤯
It was found that a loss of the 7q chromosome on the CUX1 gene causes a greater expression of the CFLAR gene, which contains a protein that restricts apoptosis (cells dying off when they are told to). This can potentially provide cancer cells with a route to escape and multiply exponentially with the help of this genetic mutation.
As a result, intensive research is being done to target this CFLAR gene as well as the pathways that cancer uses to escape and metastasize in order to provide a more effective and sustainable treatment option for patients.
Though there are no currently approved medications, Dr. Emmanuelle Supper put it best when describing the massive impact this discovery can have in saying:
“By building on our previous analysis, this research has allowed us to gain crucial information about the development of this disease, and would not have been possible without the new and exciting CRISPR/Cas9 and genome sequencing technologies that enable us to investigate genetic weaknesses in cancer. Understanding more about the genetic basis of disease, and how multiple mutations come together to cause blood cancer is vital if we hope to save lives in the future.”
Acute Lymphoblastic Leukemia (ALL)
While standard treatments are mainly chemotherapy, radiation therapy, and stem-cell transplants, lots of research is being done in the field of targeted and immunotherapy to make them more mainstream and viable options for ALL.
Pediatric (childhood) leukemias sometimes occur due to gene fusions that can accelerate cancer growth. This is when two previously independent genes come together to create one hybrid gene, which can occur as a result of translocation (a change in where genes are found), interstitial deletion (genes getting removed from the inside), or chromosomal inversion (backwards).
One type of target drug to specifically treat children with solid tumours is called larotrectinib (Vitrakvi). Clinical trials are under ways to test this drug and others like it on children with leukemia to prevent gene fusion.
For immunotherapy using CAR T-cells, though it is currently only used for leukemia that has relapsed or is resistant to standard treatment, research in the Children’s Oncology Group (COG) is underway to include it in the standard treatment protocol. Since many leukemia patients don’t have healthy enough T-cells to be collected, an “off-the-shelf” version of this therapy is being looked into so as to no longer need patient blood samples.
Two new drugs for immunotherapy are also in clinical trials to strengthen the immune system. The first, blinatumomab (Blincyto), has shown to be more effective chemotherapy by attaching to both T-cells and cancer cells. It then brings them close together, allowing for T-cells to kill the cancer cells off. The next is inotuzumab ozogamicin (Besponsa), which is being used for B-cell ALL (responsible for antibody-mediated immunity rather than T-cells for cell-mediated immunity). It consists of an antibody that binds to cancer cells and is linked to a drug that kills them off.
TL;DR
- Cancer is a genetic disease that will affect more than 1 in 3 people in their lifetime. 😖
- It develops through genetic mutations (~6 in total), and unlike healthy cells, cancerous cells do not listen to signals to stop dividing or die off.
- Cancer can arise from a multitude of factors such as lifestyle choices (ex. smoking), exposure to radiation or electromagnetic fields, and even simply one’s inherited genes from their biological parents. 🧬
- A specific cancer like leukemia (a blood cancer) is one of the only cancer types more common in children than adults, with about 74% of those childhood leukemia diagnoses being Acute Lymphoblastic Leukemia (including my own). 🎗
- Leukemia is much more common in boys compared to girls, and has 3 main stages of treatment: induction, consolidation, maintenance.
- The 5 different types of treatment for leukemia are: chemotherapy, radiation therapy, immunotherapy, targeted therapy, and cell transplants. Each of them represents a different battle strategy in the fight against cancer. 🥊
- As science advances, new evidence is being found and researched to better understand this horrific disease. Everything from how it forms, to why it’s more common for certain demographics, and some emerging options/technologies for more effective treatments. 💊
Conclusion
There is no shortage of resources out there to try and find a cure to this big ol’ “c” word. Its origins trace back to the earliest times of humanity itself, so it can seem like cancer is just a natural part of what it means to live as a human being.
An aspect of life that massively impacts over 14 million people and 400,000 children each year upon diagnosis.
Cancer, fortunately, gave me a second life. But this is not an opportunity that many kids get. It’s a dream I have in my life for there to be a cure for cancer.
And while organizations like the Make-A-Wish Foundation can provide some temporary relief by satisfying the wish of critically ill kids, there is NO wish that is more powerful than that of a healthy childhood.
I hope to one day be part of this discovery so that one day, we can finally sing “Hakuta Matata” to the Big Mama of diseases!
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Have an awesome day!!
Sources
*This section is divided into the main topics that each link focuses on which I used in this article.
Cancer Basics/Treatment
Leukemia Basics/Treatment
- https://www.cancer.gov/types/leukemia/patient/child-all-treatment-pdq#:~:text=T%2Dcell%20childhood%20acute%20lymphoblastic%20leukemia&text=Intrathecal%20and%20systemic%20chemotherapy%20are,the%20brain%20is%20also%20given
- https://www.cancer.gov/types/leukemia/research
- https://www.cincinnatichildrens.org/health/l/leukemia
- https://my.clevelandclinic.org/health/diseases/4365-leukemia
- https://www.aboutkidshealth.ca/article?contentid=2826&language=english
- https://together.stjude.org/en-us/about-pediatric-cancer/types/leukemia.html
- https://www.cancer.org/cancer/leukemia-in-children.html
- https://cancer.ca/en/cancer-information/cancer-types/leukemia-childhood/what-is-childhood-leukemia
- https://www.healthline.com/health/leukemia/aml-vs-all
- https://www.livescience.com/why-some-leukemia-mostly-affects-children.html
- https://www.nhs.uk/conditions/acute-lymphoblastic-leukaemia/
- https://www.cedars-sinai.org/health-library/diseases-and-conditions---pediatrics/l/leukemia-in-children.html
Cancer/Leukemia Causes
- https://pubmed.ncbi.nlm.nih.gov/19454804/#:~:text=Leukaemia%20was%20the%20first%20cancer,ten%20years%20after%20radiation%20exposure
- https://www.cancer.gov/types/leukemia/hp/child-all-treatment-pdq#_TrialSearch_1_sid_1_toc
- https://www.cancer.org/content/dam/CRC/PDF/Public/8694.00.pdf
- https://www.sciencedaily.com/releases/2018/05/180521131746.htm
- https://pubmed.ncbi.nlm.nih.gov/10391104/
- https://link.springer.com/article/10.1007/s002770050507?noAccess=true
- https://www.harvardmagazine.com/2017/03/why-is-cancer-more-common-in-men#:~:text=A%20physician%2Dresearcher%20who%20studies,located%20on%20the%20X%20chromosome
- https://cancer.ca/en/cancer-information/cancer-types/leukemia-childhood/risks
- https://www.livescience.com/why-some-leukemia-mostly-affects-children.html
Future of Cancer/Leukemia Treatment
- https://www.cancer.org/cancer/leukemia-in-children/about/new-research.html
- https://www.fredhutch.org/en/news/center-news/2016/04/advanced-leukemia-remission-immunotherapy.html
- https://www.sciencedaily.com/releases/2021/04/210430093212.htm
- https://www.webmd.com/cancer/lymphoma/news/20210402/combo-therapy-helps-beat-a-common-childhood-leukemia
- https://www.cancer.gov/about-cancer/treatment/research/car-t-cells
- https://www.webmd.com/cancer/lymphoma/news/20211214/drug-can-keep-leukemia-in-remission-for-years-in-younger-patients
