Juvenile myelomonocytic leukemia in the molecular era: a clinician’s guide to diagnosis, risk stratification, and treatment
Juvenile myelomonocytic leukemia is a rare disorder that has characteristics of myeloproliferative disorders and myelodysplastic syndromes. In this review by Loh and colleagues, the diagnosis, risk stratification, and treatment are examined now that molecular tools are available.
Poly(ADP-ribose) polymerase 1 (PARP1) is a key mediator of DNA damage repair and plays an important role in several malignancies. The role of this enzyme in the pathophysiology and prognosis of patients with acute myeloid leukemia/myelodysplastic syndrome is detailed in this review by Viniou and colleagues, highlighting the potential of targeting this pathway in the future for the treatment of these disorders.
CNS involvement in AML at diagnosis is rare and does not affect response or survival: data from 11 ECOG-ACRIN trials
The need for a cerebrospinal fluid examination in patients with acute myeloid leukemia (AML) and prognostic significance of central nervous system (CNS) involvement remains controversial. In this article, Ganzel et al report on a large, robust dataset by the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN), which spans 4 decades and demonstrates that CNS disease at diagnosis, per se, does not signify poor prognosis with current therapies. This is a clinically relevant article that will help guide the clinical management of CNS disease in AML.
In this article, Bruce and colleagues build on their previous work utilizing ex vivo expanded innate lymphoid type 2 (ILC2) cells to decrease graft-versus-host disease (GvHD) severity and mortality in mouse models of MHC-mismatched allo-BMT by exploring the use of third party ILC2 cells. They report a modest in vivo protective activity with a regimen of 4 weekly ex vivo ILC2 infusions after allo-BMT, which was most optimal when administered as prophylaxis. Mechanistically, the authors documented decreased numbers of IFNg-producing T cells in the gut in ILC-infused allo-BMT recipients, as well as a requirement for amphiregulin and IL-13 expression in ILCs to mediate their effect. It is hoped that these preclinical results will now lead to the design of human clinical trials infusing expanded off-the-shelf third party ILC2s in the prophylactic and treatment settings.
Immunotherapy has burst onto the scene for the treatment of many malignancies, including hematopoietic cancers. Lesch and Gill review the various forms of immunotherapy that have reached the clinic, highlighting their pros and cons. We hope that this review puts this complex field in perspective and informs both skilled practitioners and the curious.
Cytokine-induced natural killer cell training is dependent on cellular metabolism and is defective in obesity
Cytokine-induced memory-like, or trained, natural killer (NK) cells are becoming an important cell therapy approach for the treatment of patients with hematological malignancies. This article seeks to address two fundamental questions. (1) Is metabolic reprogramming required during NK cytokine “training,” a process in which NK cells can be programmed to rapidly respond to a secondary stimulus, producing cytokines with antitumor potential? (2) Since NK cells from obese individuals are characterized by poor cytokine production and diminished antitumor function, is metabolic reprogramming a barrier to NK function in obese individuals, and if so, can their NK cells be adapted and “trained” to differentiate into functional memory NK cells? These overarching questions are highly appealing to the adoptive immunotherapy readership with important implications regarding our understanding of potential barriers to efficacy in certain patient groups (ie, obese patients).