Leaders in blood cancer research and care share latest advances at ASH annual meeting

ASH Plenary Session

Scientists and physicians who focus on blood cancers, also called hematological – or heme – malignancies, gathered in Orlando, Florida for the 57th American Society of Hematology Annual Meeting and Exposition from December 5-8, 2015. This conference is the world’s premier scientific meeting in heme malignancies, and drew more than 25,000 attendees from around the world. From the latest discoveries of the underlying biology of blood cancers to clinical trials of the newest personalized therapies for leukemia, lymphoma and multiple myeloma, the conference brings together the brightest minds to share data and move the field forward. Many of the advances presented here will shape the care that patients receive tomorrow.

Among the outstanding science presented at the meeting, four major scientific themes emerged: 1) novel understanding of biology; 2) precision medicine challenges in acute myeloid leukemia (AML); 3) opportunities and challenges in multiple myeloma; and 4) drug discovery and new therapies. University of Chicago Medicine Comprehensive Cancer Center scientists and clinicians, as well as trainees, contributed significantly to the wealth of information presented in each of these areas, and many others. A complete list of presentations involving our researchers is listed here, and some highlights are described below.

Biology

Basic research into the fundamental, underlying biology of what makes normal cells become malignant and the mechanisms that control disease progression provides a foundation for the future development of new and more effective drugs.

Dr Churpek

Jane Churpek, MD

Jane Churpek, MD, presented data from a collaborative project with fellow Comprehensive Cancer Center faculty members Lucy Godley, MD, PhD, Michelle Le Beau, PhD, and James Vardiman, MD, that outlined a role for the breast cancer gene, BRCA1, in heme malignancies. Using a mouse model, they found that deletion of the gene, which encodes a protein important for repairing DNA sequence changes and other DNA abnormalities, causes bone marrow failure, lymphomas, and leukemia.

Angela Stoddart, PhD, a research associate in Le Beau’s laboratory, gave a talk on the role of the microenvironment (surrounding tissue) of hematopoietic stem cells and bone marrow in leukemia. Again using a mouse model, the research team, which also included Jason Cheng, MD, PhD, found that loss of a specific set of genes (Apc, Egr1, and p53) caused leukemia upon exposure to a cytotoxic (cell killing) agent. This work establishes a model to understand the development of blood cancers that occur as a result of exposure to chemotherapy, which could help identify new anticancer drug targets in stem cells and the bone marrow.

Jill de Jong, MD, PhD, presented recent work from a zebrafish model of T cell acute lymphoblastic leukemia (ALL). Her team found that histone deacetylase 1 (hdac1), which modifies DNA structure and gene expression, controlled the number of leukemia initiating cells present in the tumor model. The researchers subsequently identified some potential genes targets regulated by hdac1 in these cells.

In an example of outstanding collaborative team science that garnered considerable attention, a study involving Wendy Stock, MD, with a large team from St. Jude Children’s Research Hospital among others, identified a distinct subtype of B progenitor ALL in children, adolescents and young adults. They found that this subtype had a distinct gene expression profile and favorable survival outcome. The team identified novel genetic alterations of the ERG gene that drove abnormal expression of the ERG transcription factor (protein that binds to specific DNA sequences) and caused leukemia.

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Acute Myeloid Leukemia

Despite the fact that our understanding and treatment of AML has improved considerably in recent years, there is still need for improvement. For example, many patients experience relapse or disease that doesn’t respond or has become resistant to treatment (i.e., refractory).

In a Plenary Session presentation that received much attention, results were presented from an international randomized trial with a targeted drug, midostaurin, in patients with a specific type of newly diagnosed AML. Richard Larson, MD, led the Comprehensive Cancer Center’s involvement in the trial, which showed improved event-free and overall survival in patients with FLT3-mutant AML who received this drug – a tyrosine kinase inhibitor – in addition to standard chemotherapy.

Research from Jason Cheng, MD, PhD, focused on the action of drugs that impact epigenetics, a mode of gene structure/function regulation not involving changes in DNA sequence, in myelodysplastic syndromes (MDS) and AML. He presented findings from a study also involving Comprehensive Cancer Center faculty Yuan Li, MD, John Anastasi, MD, Richard Larson, MD, and James Vardiman, MD, that found drug-sensitive DNA structures in different MDS/AML subtypes and identified a set of factors important for these structures and resulting disease-specific gene expression.

Resident Yasmin Karimi, MD, presented the results of a phase I trial of the drug azacitidine combined with chemotherapies cytarabine and mitoxantrone for remission induction in high-risk AML. The research team, including Comprehensive Cancer Center investigators Richard Larson, MD, Olatoyosi Odenike, MD, Wendy Stock, MD, Michael Thirman, MD, Hongtao Liu, MD, PhD, Andrew Artz, MD, and Lucy Godley, MD, PhD, showed that this drug combination was well tolerated and had impressive clinical activity. They also identified an appropriate dosing for subsequent trials.

Myeloma

This is a very exciting time in the treatment of multiple myeloma, with game-changing treatments being approved recently. Nevertheless, there is room for improvement, namely for those patients with relapsed or refractory disease.

Dr Jakubowiak

Andrzej Jakubowiak, MD, PhD

Andrzej Jakubowiak, MD, PhD, presented the results of a multicenter Multiple Myeloma Research Foundation phase I trial of a new anticancer drug in relapsed/refractory myeloma. This agent, selinexor, restores the activity of factors that block cell growth by controlling their location within cells. His team, including other Comprehensive Cancer Center investigators Todd Zimmerman, MD, and Theodore Karrison, PhD, found that selinexor, in combination with the proteasome inhibitor carfilzomib and steroid dexamethasone, showed promising activity with 75 percent partial response or better with no unexpected side effects. These findings suggest this drug may overcome carfilzomib treatment resistance.

In a study of 15.5 million adults in Taiwan, Brian Chiu, MD, reported a link between the long-term use of certain statin drugs, a class of cholesterol-lowering drugs that also act on the immune system, and decreased risk of multiple myeloma. His research team included Habibul Ahsan, MD.

New Therapies

There are many ongoing clinical trials – of all phases – testing new agents for heme malignancies, and this work is essential to establish the safety and effectiveness of novel treatments before they can become the new “standard-of-care” treatment.

Fellow Natalie Galanina, MD, presented results of a University of Chicago phase II consortium trial of inhibiting the MEK signaling protein with a drug called selumetinib in patients with relapsed/refractory diffuse large B-cell lymphoma. The team, which included Comprehensive Cancer Center faculty Walter Stadler, MD, Kenneth Cohen, MD, Sonali Smith, MD, and Theodore Karrison, PhD, found that this drug was not well tolerated and had limited clinical activity, suggesting that other, related targets should be considered in this patient population.

In a collaborative project between pediatric hematologist James LaBelle, MD, PhD, and Matthew Tirrell, PhD, dean and founding Pritzker Director of the Institute for Molecular Engineering, medical student Joseph Bellairs described the development of novel anticancer agents. These short protein sequences, packaged so that they would be stable and enter cells efficiently, were found to potently induce cancer cell death, and will be evaluated further in animal cancer models.

Other notable examples of the Comprehensive Cancer Center’s presence at the meeting included Wendy Stock, MD, who moderated a press event on “Personalized Approaches to Pediatric Blood Diseases”, Richard Larson, MD, who served as chair and speaker in a session on “Managing Typical and Atypical Chronic Myeloid Leukemia,” and Sonali Smith, MD, who moderated a session on “Clinical Autologous Transplantation.” Additionally, Andrew Artz, MD, Michael Thirman, MD, and Jane Churpek, MD, delivered oral presentations in the Friday Scientific Session of the conference on frailty in stem cell transplantation, a model of MLL-AF4-driven leukemia, and inherited bone marrow failures syndromes, respectively.

Social media has had a growing presence and impact at scientific conferences, and the 2015 ASH Annual Meeting was no exception. Before the morning on the final day, there had been more than 18,000 tweets using the meeting’s hashtag (#ASH15), with more than 3,000 Twitter participants and 129 average tweets per hour. Moreover, the session on social media for hematologists was very well attended and engaged more users at all levels from social media beginners to experts.

About Kathleen Goss (30 Articles)
Kathleen Goss, PhD, is the Director for Strategic Partnerships and senior science writer at the University of Chicago Medicine Comprehensive Cancer Center.
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