Issue Archive

Introduced by Associate Editors Thomas Coates and Irene Roberts, this review series focuses on globin disorders, covering advances in our understanding of globin gene biology that have already been translated into meaningful benefit for patients as well as those with the potential for future therapeutic impact. Written by leaders in the field of α- and β-globin study, these articles collectively highlight the rewards for patients that can arise from decades of dedicated research.

The origins of childhood B-cell acute lymphoblastic leukemia (B-ALL) often begin during embryonic life when germ line or somatic mutations give rise to preleukemic stem cells. Viral infections have been demonstrated to promote leukemia development by causing second mutations. In this Plenary Paper, Farrokhi and colleagues now present the first evidence that early postnatal infection provokes an immune response that protects the host from developing B-ALL by depleting preleukemic cells. These data help explain why so few children born with preleukemic mutations subsequently suffer B-ALL.

Introduced by Associate Editors Thomas Coates and Irene Roberts, this review series focuses on globin disorders, covering advances in our understanding of globin gene biology that have already been translated into meaningful benefit for patients as well as those with the potential for future therapeutic impact. Written by leaders in the field of α- and β-globin study, these articles collectively highlight the rewards for patients that can arise from decades of dedicated research.

Introduced by Associate Editors Thomas Coates and Irene Roberts, this review series focuses on globin disorders, covering advances in our understanding of globin gene biology that have already been translated into meaningful benefit for patients as well as those with the potential for future therapeutic impact. Written by leaders in the field of α- and β-globin study, these articles collectively highlight the rewards for patients that can arise from decades of dedicated research.

Introduced by Associate Editors Thomas Coates and Irene Roberts, this review series focuses on globin disorders, covering advances in our understanding of globin gene biology that have already been translated into meaningful benefit for patients as well as those with the potential for future therapeutic impact. Written by leaders in the field of α- and β-globin study, these articles collectively highlight the rewards for patients that can arise from decades of dedicated research.

Introduced by Associate Editors Thomas Coates and Irene Roberts, this review series focuses on globin disorders, covering advances in our understanding of globin gene biology that have already been translated into meaningful benefit for patients as well as those with the potential for future therapeutic impact. Written by leaders in the field of α- and β-globin study, these articles collectively highlight the rewards for patients that can arise from decades of dedicated research.

Relapsed mantle cell lymphoma (MCL) portends poor prognosis, but with multiple new agents showing encouraging response rates, data on long-term outcomes are essential. Handunnetti and colleagues report on the 7-year follow-up of the first phase 2 trial of patients heavily pretreated with the combination of ibrutinib and venetoclax, documenting 30% 7-year progression-free survival and durable remissions after treatment cessation in the majority of patients who achieved measurable residual disease–negative complete remission. With the median time-off therapy approaching 5 years, this trial provides key evidence for the use of response-informed regimens combining BCL2 and Bruton tyrosine kinase inhibitors in MCL.

Primary hemophagocytic lymphohistiocytosis is a hyperinflammatory disorder caused by biallelic loss-of-function mutations in genes required for CD8 T-cell and natural killer (NK)–cell cytotoxicity. Diagnosis requires a constellation of clinical and laboratory findings, including functional impairment in NK-cell cytotoxicity, which can be challenging. Chiang et al report on an encouraging novel in vitro assay that quantifies cytotoxic lymphocyte exocytosis more accurately than standard K562 cell line–based assays, warranting further assessment for routine incorporation into diagnostic workups.

Radpour and colleagues uncover a novel mechanism by which leukemia stem cells (LSCs) hijack T helper (Th) cells in the bone marrow of patients with acute myeloid leukemia (AML), promoting their own expansion and contributing to disease progression. Using transcriptomic profiling, unbiased high-throughput correlation network analyses, and functional assays of patient bone marrow, the authors identified that interleukin-9 (IL-9) secreted by AML LSCs epigenetically activated CD4⁺ T cells, inducing Th1-skewing and the secretion of interferon gamma and tumor necrosis factor α, which in turn enabled LSC expansion. These data highlight IL-9 as a potential therapeutic target.

Liver graft-versus-host disease (GVHD) frequently presents as cholestasis, commonly associated with degenerative changes of the portal bile ducts. Hasegawa et al report that liver macrophage–derived transforming growth factor-β (TGF-β) injures bile duct stem cells in mice during GVHD, resulting in impaired hepatic regeneration and function, explaining the phenotypic features seen in patients. The authors’ preclinical data argue for further examinations of the potential clinical utility of TGF-β signaling inhibitors to reduce hepatic dysfunction during GVHD.