Best of ASH 2015: From Emerging Concepts in Biology to New Therapies

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Andrew W. Roberts, MBBS, PhD, scientific program co-chair summarizes the best research presented at the 57th American Society of Hematology Annual Meeting.
Andrew W. Roberts, MBBS, PhD, scientific program co-chair summarizes the best research presented at the 57th American Society of Hematology Annual Meeting.

Emerging concepts in biology. Precision medicine challenge in acute myeloid leukemia. Trials and tribulations in melanoma. New therapies.

These were the 4 themes Andrew W. Roberts, MBBS, PhD, scientific program co-chair of the 57th American Society of Hematology (ASH) Annual Meeting identified in his “Best of ASH” summary.1

Dr Roberts, of the Royal Melbourne Hospital & Walter and Eliza Hall Institute, University of Melbourne in Melbourne, Australia, highlighted several abstracts representative of each theme.

Emerging Concepts in Biology

The first study found that 9p24.1/PD-L1/PD-L2 alterations were a defining feature of classical Hodgkin lymphoma, with copy gain and amplifications the most frequent changes.

Patients with advanced stage disease had an increased incidence of this amplification, which was associated with adverse outcomes. Margaretha G.M. Roemer, MS, Dana-Farber Cancer Institute in Boston, MA, and colleagues found that “near universal 9p24.1 genetic alterations likely explain the efficacy of PD-1 blockade in classical Hodgkin lymphoma” (Abstract 176).

Yoshihiro Hayashi, MD, PhD, Cincinnati Children's Hospital Medical Center in OH, and colleagues created a working model to explain how driver aberrations activate HIF-1α signaling in both myelodysplastic hematopoietic stem/progenitor cells (HSPCs) and mature cells.

This activated signaling gives clonal expansion advantage to MDS HSPCs and, in mature cells, causes dysplasia, activated inflammatory immunity, and ineffective erythropoiesis (Abstract 303).

Dan A. Landau, MD, PhD, Dana-Farber Cancer Institute and the Broad Institute in Boston, MA, and colleagues introduced “a framework for dissecting evolutionary dynamics with primary patient samples,” Dr Roberts reported. The team used quantitative clonal dynamics to define mechanisms of chronic lymphocytic lymphoma evolution, with the goal of applying these methods in the context of targeted therapy (Abstract 362).

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In attempting to define the genetic basis of “novel” acute lymphoblastic leukemia, Charles G. Mullighan, MBBS (Hons), MSc, MD, St. Jude's Children's Research Hospital in Memphis, TN, found that oncogenic ERG isoform characterizes a distinct subtype of B-progenitor acute lymphoblastic leukemia (ALL), with ERG deletions present in 56% of cases (Abstract 693). Therefore, “accurate diagnosis of ERG ALL requires integrated transcriptomic and genetic profiling.”

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