We all know that cancer is essentially when cells in a part of the body begin to grow out of control. In the case of acute myeloid leukaemia (AML), it starts in the soft inner part of certain bones called the bone marrow, where new blood cells are made.
Normally, the bone marrow makes blood stem cells (immature cells) that become mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. A myeloid stem cell becomes one of 3 types of mature blood cells: red blood cells (for oxygen and carbon dioxide transport), white blood cells (to fight off infection and diseases), and platelets (to form blood clots to stop bleeding). A lymphoid stem cell becomes a white blood cell.
In AML, the myeloid stem cells become a type of immature white blood cell called myeloblasts (or myeloid blasts). Myeloid blasts are abnormal white blood cells and are not healthy. Sometimes, too many stem cells become abnormal red blood cells or platelets (leukaemia cells or blasts).
Over time, these cells build up in the bone marrow and blood resulting in less room for healthy white blood cells, red blood cells, and platelets. When this happens, infection, anaemia, or easy bleeding may occur. It gets worse when the leukaemia cells spread outside the blood to other parts of the body, including the central nervous system (brain and spinal cord), skin, and gums.
Visible Symptoms of AML
The early signs and symptoms of AML can often be similar to those caused by the flu virus or other common diseases. Patients usually experience fever, shortness of breath, fatigue and tiredness.
Other signs include easy bruising and bleeding. The skin may also exhibit petechiae – flat, pinpoint spots under the skin caused by that bleeding.
In some cases, patients experience weight loss due to lack of appetite.
Risk Factors
There are many risk factors associated with AML, the most notable of which is the greater prevalence in males, but there are also habitual risk factors such as smoking, especially after the age of 60. Patients who have a history of blood disorders are at greater risk of developing AML.
A history of treatment with chemotherapy or radiation therapy can also be a risk factor, as well as any prior exposure to radiation or to the chemical benzene.
AML by the Numbers
AML is one of the most common types of leukaemia diagnosed in adults. Statistically, in the United States, it makes up 32% of all adult leukaemia cases.
Still, AML is rare overall, only accounting for about 1% of all cancers, and 1.8% of all cancer deaths. The average age of patients first diagnosed with AML is around 68 years old and it is uncommon for patients under the age of 45.
AML, however, can occur in children. In the US, about 500 cases of juvenile AML are reported each year.
Current Treatments and Challenges for AML
Timing is critical to combatting AML as the disease can progress quickly if not treated. It’s important for patients to start treatment as soon as possible after the diagnosis is made.
The main treatment for AML is usually chemotherapy, sometimes along with a targeted therapy drug. This might be followed by a stem cell transplant. While the option of surgery and radiation therapy are not major treatments for AML, they may be considered depending on the circumstances.
Current treatments have shown 5-year overall survival rates of about 60% in children and 30-40% in adults. However, the high incidence of relapse in both children and adults remains a great challenge today.
Here’s an example of why: current methods of AML treatment largely rely on the use of aggressive chemotherapy that is aimed to induce cancer remission rather than cure it. While this treatment method is moderately successful for some patients, relapse is frequent. Most patients, especially those over 60 years of age, rapidly succumb to the disease.
In fact, the prognosis for older patients with AML is poor: very few achieve remission and for those that don’t the only real option is palliative care.
The Search for New Treatments
AML patients need more advanced and precise treatment methods. Medical research and development in this field is often regarded as a dead end activity, mainly because trials of new drugs are rarely successful. Furthermore, AML is widely perceived as an untreatable and inevitably fatal condition for older patients by most doctors.
In recent years, however, targeted oncology is taking centre stage by addressing AML treatments with greater efficacy. New trials (and approvals) within the past year have been significantly impacting the treatment landscape.
Newer targeted drugs specifically attack some of the gene changes seen in AML cells and are now becoming an important part of treatment for patients.
Oncolytic Viral Therapy
Oncolytic viral therapy is a new and promising strategy against cancer. It involves treating cancer using a modified virus. These modified viruses (known as oncolytic viruses or OVs) will only infect cancer cells and not in normal cells, making it non-pathogenic to the patient. Ongoing research has already proven it to be potentially effective for the treatment of solid tumours and haematological malignancies
The treatment method usually involves intravenous delivery of the OVs into the patient, specifically into the tumour area. This activates, or boosts, the patient’s immune system so that it can facilitate a strong and durable response against the tumour itself.
Furthermore, OVs infect the tumour so that they can replicate as the cancer cells multiply, leading to lysis (destruction) of the tumour mass. This makes OVs self-sufficient and, as such, the treatment becomes more effective as it progresses.
One such example of an OV treatment is by OncoMyx Therapeutics. They are currently working on a modified poxvirus, called myxoma virus (MYXV), as an oncolytic agent to treat a wide variety of cancer targets.
Epigenetic Therapy
Epigenetic therapy is a relatively new concept. Imagine this: the ‘genetic’ pathway essentially involves cells reading the genes so that they can replicate. Epigenetic means ‘above’ or ‘on top of’ genetics, implying that it can modify the DNA temporarily to turn genes ‘on’ or ‘off’. These modifications do not alter or change the DNA sequence, they simply affect how cells ‘read’ the genes.
AML is a disease that is influenced by epigenetic mechanisms, and epigenetic therapy, in this case, offers a potential way to influence those pathways directly, without the risk of suffering the potential side-effects from genetic modification.
Take, for example, the IMG-7289 (by Imago Biosciences™). It is a small molecule that inhibits the enzyme responsible for sustaining self-renewal in cancer stem/progenitor cells in the bone marrow. The enzyme inhibited is lysine-specific demethylase 1 (LSD1). The results are promising – high in-vivo efficacy in patients during clinical trial, showing very little to no growth of cancer stem/progenitor cells.
Conclusion
AML is the second most common type of leukaemia diagnosed in the United States. While chemotherapy is still the main treatment for AML, it rarely succeeds in its intended purpose which is to drive cancer remission. Medical researchers are now working on advanced, targeted methods of therapy, which can improve the odds for AML patients. With the recent trials and approvals in the past couple of years, patients suffering from AML now have more treatment options available. It is giving real hope to patients who previously had little.
Xeraya Capital in the Fight Against Cancer
Xeraya Capital’s commitment to bettering the chances of AML patients is realised in the recent collaboration with Imago Biosciences™ and OncoMyx Therapeutics. We join experienced investors in advancing these therapeutic pipelines with the ultimate goal of delivering new treatment options to cancer patients.
Sources:
1. https://www.stjude.org/disease/acute-myeloid-leukemia.html
2. https://www.cancer.gov/types/leukemia/patient/adult-aml-treatment-pdq
3. https://www.hindawi.com/journals/jo/si/820396/cfp/
4. https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340870/
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932159/
7. https://www.livescience.com/37703-epigenetics.html
8. https://www.cancer.org/cancer/acute-myeloid-leukemia/about/new-research.html
