Issue Archive

EVI1-rearranged acute myeloid leukemia is an aggressive malignancy associated with chemotherapy resistance and poor prognosis. In this Plenary Paper, Schmoellerl and colleagues used both human and murine models and genome-wide CRISPR screens to characterize the downstream targets of EVI1. They identified ERG as a direct transcriptional target of EVI1 that blocks differentiation and facilitates self-renewal, suggesting a regulatory pathway potentially useful for targeted therapy.

Falchi and colleagues review the development of and clinical experience with bispecific antibodies, a class of T-cell redirecting drugs with excellent activity in patients with relapsed/recurrent B-cell non-Hodgkin lymphoma.

Primary therapy for acute graft vs host disease (aGVHD) is systemic corticosteroids. Etra et al report on the results of a nonrandomized study of monotherapy with the selective JAK1 inhibitor itacitinib in 70 patients with low-risk aGVHD, compared to a contemporaneous cohort of steroid-treated patients. Responses to itacitinib were comparable to steroids (89% vs 86% at 28 days), with fewer serious viral and fungal infections with itacitinib, providing support for a randomized clinical trial in low-risk GVHD.

TGF-β1 has been implicated in promoting fibrosis in primary myelofibrosis (PMF), which is secreted ubiquitously but must be activated, and activation is cell-type specific. Lecomte and colleagues report that TGF-β1 is activated by GARP expressed by regulatory T cells, and an antibody that blocks TGF-β1 activation reduced fibrosis in a mouse model of PMF.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease that is supported by the tumor microenvironment. Cappelli and colleagues used primary T-ALL patient cells cocultured with endothelial cells (ECs) to delineate the role of ECs in chemoprotection of T-ALL cells and to screen for drugs to overcome that resistance. The authors identified 5 agents that improve survival in mouse xenografts, suggesting that the platform can be used to identify compounds that target tumor cell–EC interactions.

Two articles focus on the use of next generation sequencing (NGS) for the assessment of minimal residual disease (MRD). In the first article, Hengeveld et al report on a novel, academically developed immunoglobulin sequence-based NGS assay for quantitative detection of MRD in chronic lymphocytic leukemia (CLL). This technique, made available to other laboratories, has a range of detection that is more sensitive than conventional techniques and provides accurate prognostic stratification of patients with CLL. In the second article, Svaton et al compared allele-specific oligonucleotide polymerase chain reaction to NGS assay of immunoglobulin or T-cell receptor markers in pediatric B-cell acute lymphoblastic leukemia (ALL), again confirming that this is a reliable alternative for assessing MRD.

Two articles focus on the use of next generation sequencing (NGS) for the assessment of minimal residual disease (MRD). In the first article, Hengeveld et al report on a novel, academically developed immunoglobulin sequence-based NGS assay for quantitative detection of MRD in chronic lymphocytic leukemia (CLL). This technique, made available to other laboratories, has a range of detection that is more sensitive than conventional techniques and provides accurate prognostic stratification of patients with CLL. In the second article, Svaton et al compared allele-specific oligonucleotide polymerase chain reaction to NGS assay of immunoglobulin or T-cell receptor markers in pediatric B-cell acute lymphoblastic leukemia (ALL), again confirming that this is a reliable alternative for assessing MRD.

Makishima and colleagues report on a comprehensive characterization of 346 patients with myeloid neoplasms (MN) in the context of germ line DDX41 mutation and 525 first-degree relatives. Development of MN increased rapidly after age 40, with 49% developing MN by age 90. Computations were different from DDX41 wild-type patients, and when present, did not worsen the prognosis associated with this subset of MN.