Acute myeloid leukemia has at least 11 different subtypes


Acute myeloid leukemia has at least 11 different subtypes

Rather than being one disease, acute myeloid leukemia is at least 11 different conditions, each with a different genetic profile and clinical features. This is the finding of what has been hailed as a "groundbreaking" new study published in the New England Journal of Medicine.

Researchers say AML is at least 11 different diseases, all of which have different genetic alterations and clinical features.

Study co-leader Dr. Peter Campbell, of the Wellcome Trust Sanger Institute in the United Kingdom, and colleagues say their findings may explain why young people with acute myeloid leukemia (AML) show significant differences in survival.

Furthermore, the results could lead to improvements in the way patients are diagnosed and treated.

AML is an aggressive form of blood cancer that starts in the bone marrow, before - in most cases - rapidly moving to the bloodstream. It can also spread to the lymph nodes, spleen, central nervous system (CNS), liver, and other parts of the body.

According to the American Cancer Society (ACS), there will be around 19,950 new cases of AML diagnosed in the United States this year. While it is most common among adults aged 45 and older, it can affect people of all ages.

AML treatment responses vary

Chemotherapy is normally the first-line treatment for AML, and this may be followed up with a stem cell transplant.

However, treatment outcomes for AML patients vary. Dr. Campbell and colleagues note that while most patients respond to chemotherapy initially, many experience disease relapse; the 5-year survival rate stands at around 26 percent after an AML diagnosis.

But why do some people with AML respond well to treatment while others do not? Previous research has suggested it is down to the array of different genetic mutations that drive AML development.

"There are many leukemia genes, most of which are infrequently mutated, and patients typically have more than one driver mutation," the authors explain.

"The disease evolves over time, with multiple competing clones coexisting at any time. These discoveries are revealing the biologic intricacies of AML, but how they inform clinical practice is unclear."

At least 11 AML subgroups identified

For their study, the team set out to investigate how the genetic diversity of AML influences the physiological course of the disease.

Using patient data from three multicenter clinical trials involving 1,540 patients with AML, the researchers analyzed and sequenced 111 genes known to cause the disease.

They matched this data with information on patients' treatment and survival, with the aim of identifying specific patterns of driver mutations that influence clinical outcomes.

While the researchers did identify some common genetic themes across all AML patients, they found they could also divide patients into at least 11 different groups, each with unique driver mutations and distinct clinical features.

The authors say their study - representing the first detailed analysis of how genetic complexity in a cancer can influence clinical outcomes - may help explain the differences in treatment outcomes for patients with AML.

Two people may have what looks like the same leukemia down the microscope, but we find extensive differences between those leukemias at the genetic level. These genetic differences can explain so much of why one of those patients will be cured, while the other will not, despite receiving the exact same treatment.

We have shown that AML is an umbrella term for a group of at least 11 different types of leukemia. We can now start to decode these genetics to shape clinical trials and develop diagnostics."

Dr. Peter Campbell

As well as paving the way for new diagnostic techniques for AML, the researchers believe their findings may open the door to more personalized treatment.

"For the first time we untangled the genetic complexity seen in most AML cancer genomes into distinct evolutionary paths that lead to AML," says joint first author Dr. Elli Papaemmanui, of the Sanger Institute and the Memorial Sloan Kettering Cancer Center in New York, NY.

"By understanding these paths we can help develop more appropriate treatments for individual patients with AML. We are now extending such studies across other leukemias."

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Section Issues On Medicine: Disease