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In this issue’s Blood Advances Talk, Lapidot and Golan discuss how changes in daily light regulate hematopoiesis. This fascinating mechanism helps control the process of maintaining the hematopoietic stem cell pool while promoting sufficient differentiation to supply adequate numbers of functional blood cells. We hope you enjoy listening to this interesting topic. 



Sperandio and colleagues review the ontogeny of platelet function during development, highlighting a number of important biological insights and how these novel findings impact platelet transfusion therapy in neonates.


The treatment of older patients with acute myeloid leukemia (AML) presents critical challenges due to toxicities and comorbid medical conditions. Garcia-Manero and colleagues explore the combination of pracinostat, a potent pan-histone deacetylase inhibitor, and azacytidine in older patients with newly diagnosed AML who were ineligible for standard intensive induction regimens. Their findings support this combination as one that is well tolerated with favorable complete remission and one-year survival rates justifying further evaluation of this approach.


Larsson et al tackle the critical issue of fate choice in hematopoietic stem cells. They demonstrate that HMGA2 is highly expressed on the most immature progenitor cell subsets of fetal, neonatal, and adult human hematopoiesis. They also demonstrate that modulation of this gene's expression significantly affects hematopoietic reconstitution after transplant. 


Immunotherapy has emerged as a major treatment option for a number of malignancies. Mycosis fungoides (MF) is particularly interesting since it is a disorder of malignant CD4+ T cells and infiltrates the skin that allows for ready access and characterization. Murray and colleagues evaluate and contraste MF cells with tumor infiltrating lymphocytes to highlight important differences that may have clinical implications for future immune-based therapies. 

Checkpoint inhibitors have had a major impact on the treatment of a number of malignancies. However, responses in patients with diffuse large B-cell lymphoma have been disappointing. Venstrom and colleagues explore the role of programmed death-ligand 1 expression in the tumor microenvironment that may help explain these clinical observations. 

Mutations in the complement cascade can cause a number of deadly diseases, including atypical hemolytic uremic syndrome (aHUS). While we can successfully treat aHUS by inhibiting the terminal complement pathway, such treatment can negatively impact a patient's ability to fight pathogens. Pouw et al identify a novel antibody that effectively separates the endothelial damage wrought by complement from the protection against pathogens.


Osteolytic bone disease is one of the most disabling complications of multiple myeloma that leads to significant morbidity and occasionally mortality. In the report by Seino and colleagues, the role of interleukin-34, a ligand of colony stimulating factor 1, in osteolytic bone disease in multiple myeloma is evaluated with provocative findings that potentially identifies a novel clinical target for controlling this common complication of this disease.





Yeshurun et al describe a study of a large number of acute lymphoblastic leukemia (ALL) patients using the CIBMTR registry and seek to understand 2 central questions of hematopoietic transplant for leukemia. One, is there a graft-versus-leukemia (GVL) effect that is tied to graft-versus-host disease (GVHD) for ALL? Two, if so, how does one “thread the needle” to get the best impact of GVL without undue toxicity, morbidity, and mortality from GVHD? This article provides compelling data that children and adults in first or second complete remission did best when they developed grade I or II acute GVHD (aGVHD) without chronic GVHD (cGVHD) compared to no GVHD. However, the same patients demonstrated increased nonrelapse mortality accompanying grade III or IV aGVHD, which abrogated any protection from relapse. This article reiterates the difficult balance doctors face optimizing outcomes for patients undergoing transplant for leukemia and demonstrates that severe aGVHD changes the balance against survival.



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