Research Highlight: Breakthroughs in Acute Myeloid Leukemia


April 21st was AML Awareness Day! Recent breakthroughs have led to unprecedented new treatment approvals for AML. In this highlight, we focus on some targeted therapy approaches.

Acute myeloid leukemia (AML) is an aggressive, rapidly-progressing disease in which the immature blood cells do not develop properly and grow uncontrollably. The AML cells crowd out and interfere with the number and function of normal blood cells. The need for new treatments for AML remains urgent, which is why The Leukemia & Lymphoma Society (LLS) has invested approximately one quarter of its research dollars annually in the disease, more than $100 million over the past decade. This work is complemented by our Beat AML Master Clinical Trial that has been in progress since November 2016.

While we have begun to chip away at AML, there is still much more work to be done. LLS is supporting new research through close to 80 active academic grants to explore every avenue to further improve outcomes for AML patients. These efforts include:

-Precision Medicine: methods to quickly identify the patients’ molecular alterations (mutations) and develop novel therapies that specifically target those mutations;

-Activators of cell death: as the machinery that controls cell death have been identified, new approaches to activate cell death specifically in AML cells has been achieved. Venetoclax is one of these therapies, but other control mechanisms the mediate cell death are also in development

-Novel immunotherapies: such as activators of a family of AML-killer immune cells. Chimeric antigen receptor T-cell therapy (CAR-T) is one example (See below).

-Therapies that eliminate the so-called “leukemic stem cells” which are thought to be resistant to many current treatments and results in a disease relapse

-Regulators of master control molecular switches that are aberrant in AML

-Improvement in bone marrow transplants, which would make the procedure more effective without causing severe side effects.

-Safer cytotoxic therapies that have reduced side-effects and achieve equal or better outcomes compared to standard therapies.

-A special focus on pediatric AML designed to accelerate the use of experimental therapies for this subset of patients.

-Definition and identification of pre-leukemia with the anticipation that detecting and treating patients before they develop full blown leukemia will lead to better outcomes.

With increased knowledge about AML, therapy targets have been the focus of many treatment approaches.

Precision therapy

AML is actually a complex constellation of blood cancers, each driven by different molecular alterations. As advances in genomic technology have allowed researchers to better understand the underlying causes of cancer, the one-size-fits-all treatment of AML is giving way to more targeted approaches. LLS is supporting multiple projects studying new agents with the potential to target specific mutations. The Beat AML Master Clinical Trial, an LLS-led collaboration, is testing multiple targeted therapies simultaneously at multiple cancer centers across the U.S. The trial is for newly diagnosed AML patients 60 and older. Patient bone marrow samples are analyzed to identify their subtype of disease so they can be matched with a targeted therapy for their mutation.


Immunotherapy is becoming a mainstay of many cancer treatments. Harnessing the body’s immune system is also being investigated in AML. Numerous ways to activate the immune system and enlist immune cells to kill tumor cells have been FDA-approved for solid tumors and some blood cancers. However, application of immune activators for AML still remains in the experimental stage. LLS support for directed immunotherapies includes Terry Fry, M.D. (University of Colorado) who is developing new CAR T cells specifically directing T-cells to AML tumor cells and killing such cells.

Targeting stem cells

Relapse in AML is very common and researchers suspect that minimal residual disease, small traces of cancer cells that remain after treatment, are one of the primary causes of relapse. Investigators are working to eliminate the AML cancer stem cells as a way to completely eradiate the cancer cells so the cancer does not return. This would be analogous to removing a tree at its roots compared to pruning the tree at its branches. Craig Jordan, Ph.D. (University of Colorado) leads an LLS Specialized Center of Research team taking a multi-pronged approach to eradicate cancer stem cells in AML patients.

Sign in or Register to view comments.