As reported in NewsWise, as rare diseases get their time under the microscope, growing evidence uncovers medical distinctions. New lines are drawn, delineating new disorders to be defined and classified. Finding precise types and subtypes provides useful insights into different reactions to treatment methods.
In Toronto, oncologists at Princess Margaret Cancer Centre have found that the mutation responsible for around a third of all cases of acute myeloid leukemia (AML), the NPM1 mutation, is actually made up of two unique subtypes: one that is responsive to available treatment options, the other still untreatable. Drawing this new distinction is important for finding solutions for patients with the still untreatable subtype. Providing more precise diagnosis and developing research on the subtype independently will facilitate improved accuracy of research and treatment plans.
Acute Myeloid Leukemia
Acute myeloid leukemia (AML ) is a type of rare cancer of the blood and bone marrow. An abnormal type of white blood cell is created by the bone marrow of people with AML. Over time, these cells overwhelm healthy blood cells, impeding on the bloods work. This causes patients to experience bone pain, fatigue, fevers, shortness of breath, pale skin, frequent infections and bruising, and unexpected bleeding. While various therapies exist including remission induction therapy, chemotherapy, consolidation therapy, and stem cell transplants, the effectiveness varies depending on subtype, age, and overall health.
The New Distinction: Two NPM1 Mutations
Using advanced RNA sequencing, scientists discovered that this leukemia can be triggered by two distinct mutations on the NPM1 gene; the subgroups each expressing unique NPM1 genes. The two groups were delineated by the presence or absence of a stem cell signature, inspiring the subtype labels ‘primitive’ and ‘committed’ respectively.
This difference in RNA is that it is predictive of the persons response to treatments and expected longevity. Dr. Benjamin Haibe-Kains of Princess Margaret Cancer Centre and Associate Professor of Medical Biophysics at the University of Toronto explained,
“While the NPM1 mutation is relatively common, AML is a rare disease to begin with,” He continued, “Generating enough data to be able to sequence and understand the biology of this mutation is very challenging.”
In order to breakdown their data into more precise diagnosis, they would need technology that dug deeper into their DNA. Haibe-Kains is proud of their model that is able to determine between the two subtypes of AML caused by a mutated NPM1 gene through datasets collected from patient samples.
New Treatment Plans
“Recognizing those ‘needles in a haystack’ – the small groups of patients that don’t benefit from certain treatments is critically important for improving personalized medicine,” said Dr. Mark Minden. Now that they know who the untreatable patient population is, they can focus on creating new, viable options for them.
This breakthrough though is an important step in the understanding of the distinct molecular breakdown responsible for the unique properties of the subtype. This is an important finding for the creation of personalized treatment plans with unique targeted therapies.
After identifying the subtype, the researchers were able to narrow down a list of possible treatment options, explained Dr. Haibe-Kains. They have already identified two drugs that could enter the clinical trial stage later in the research process.
They expect their result could open up more tailored protocols when it comes to dealing with the tougher cases. Now, doctors will understand right off the bat that all their first treatments can be bypassed.
Dr. Aaron Schimmer has stated that this could transform the way in which patients are treated. Doctors can better fit treatment to their patients. This could help them accomplish a major goal: providing better outcomes for patients.
