Volume 1, Issue 22


Cover Image

Cover Figure:  Three types of clonal architecture found in patients with somatic HLA loss.
See the article by Babushok et al.

WASHINGTON, October 10,  2017 – Welcome to the “Advance Notice,”  newsletter which provides highlights from issues of Blood Advances, the open-access journal of the American Society of Hematology (ASH), that  are hand-picked by Blood Advances Editor-in-Chief Robert Negrin, MD.

FLT3 mutations are common in patients with acute myeloid leukemia and are associated with inferior outcomes. A number of FLT3 inhibitors are under intense evaluation. In a Blood Advances Talk which we hope you will find interesting and informative. Mark Levis, a leading expert in this field, discusses this topic.


It has been well recognized that treatment for adolescents and young adults with leukemia is associated with better outcomes after more-aggressive pediatric treatment programs. Less is known for similar-aged patients with non-Hodgkin lymphoma. In a review article, Kahn et al discuss our knowledge of the most effective treatment strategies for these younger patients with lymphoma, as well as the gaps in that knowledge.

The bispecific monoclonal antibody emicizumab (ACE910) provides protection for patients with hemophilia A. Shima et al assessed the long-term impact of this treatment, where patients continue to receive weekly administration of emicizumab for up to 33.3 months with ongoing protection from serious bleeding.

The combination of carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance has emerged as an effective strategy for the treatment of high-risk smoldering myeloma. Mailankody et al  evaluate the longer-term effects of this treatment, as well as the role of specific mutational patterns in response.

Aplastic anemia (AA) is thought to be an autoimmune process whereby normal hematopoietic elements are attacked immunologically; however, the targets are unknown. Babushok and colleagues explored somatic HLA mutations and found them to be present in high frequency in patients with AA. In this analysis, they found a particular role for HLA class I alleles, deepening our understanding of the molecular underpinnings of this devastating disease.

Diamond-Blackfan anemia (DBA) is a rare disease characterized by a congenital failure to produce red blood cells. In many patients with this disease, a germ line mutation is found in a ribosomal protein (RP) gene. Heat shock protein 70 (HSP70) has also been implicated in disease pathogenesis. Gastou et al found that the decreased expression of HSP70 in erythroid cells is related to increased degradation of HSP70 associated with some RP mutations but not others, further demonstrating the role of this protein in DBA.

Haploidentical transplantation has emerged as an effective alternative donor source for patients without matched-sibling or unrelated donors. Robin et al report on outcomes from the European Society for Blood and Marrow Transplantation on patients with myelodysplastic syndrome who were treated with allogeneic transplantation using haploidentical donors.

Chronic graft-versus-host disease (cGVHD) is often associated with tissue fibrosis and scleroderma. Hedgehog signaling has been shown to play an important role in tissue fibrosis. Sonidegib is a selective antagonist of the hedgehog coreceptor Smoothened and was studied in a phase 1 trial for the treatment of steroid-refractory cGVHD. DeFilipp et al evaluate the initial use of this agent in a complex patient population.


Featured Visual Abstract

Two distinct CXCR4 antagonists mobilize progenitor cells in mice by different mechanisms

Mobilization of hematopoietic stem and progenitor cells has replaced bone marrow harvesting as a stem cell source in many transplant patients. The development of more effective strategies for mobilization is an important clinical goal. It is well recognized that the CXCR4/CXCL12 axis is of central importance to the mechanism of mobilization. Redpath et al studied 2 different CXCR4 antagonists to gain greater insight into the underlying mechanisms involved


Blood Advances is the open-access journal of the American Society of Hematology (ASH) (, the world’s largest professional society concerned with the causes and treatment of blood disorders.

ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.