Issue Archive

It has long been recognized that iron overload is toxic and that diagnosis and management of iron overload in patients with hematological disorders are complex and can be disease-specific. Associate Editor Thomas D. Coates presents a series that aims to deconvolute iron overload and provide advice on management. An overarching theme is that the magnitude and duration of exposure to reactive non–transferrin-bound iron, increased by ineffective erythropoiesis, transfusion, or upregulated iron absorption, determine tissue damage. Understanding this biology in a specific disease setting guides management. Coates reviews iron overload in transfusion-dependent hemoglobinopathies; Angelucci contributes insights on treating iron overload before, during, and after stem cell transplantation through discussion of 5 cases; and Leitch and Buckstein share their wisdom on treating iron overload in patients with myelodysplastic syndromes, outlining their approach in several common clinical scenarios.

It has long been recognized that iron overload is toxic and that diagnosis and management of iron overload in patients with hematological disorders are complex and can be disease-specific. Associate Editor Thomas D. Coates presents a series that aims to deconvolute iron overload and provide advice on management. An overarching theme is that the magnitude and duration of exposure to reactive non–transferrin-bound iron, increased by ineffective erythropoiesis, transfusion, or upregulated iron absorption, determine tissue damage. Understanding this biology in a specific disease setting guides management. Coates reviews iron overload in transfusion-dependent hemoglobinopathies; Angelucci contributes insights on treating iron overload before, during, and after stem cell transplantation through discussion of 5 cases; and Leitch and Buckstein share their wisdom on treating iron overload in patients with myelodysplastic syndromes, outlining their approach in several common clinical scenarios.

It has long been recognized that iron overload is toxic and that diagnosis and management of iron overload in patients with hematological disorders are complex and can be disease-specific. Associate Editor Thomas D. Coates presents a series that aims to deconvolute iron overload and provide advice on management. An overarching theme is that the magnitude and duration of exposure to reactive non–transferrin-bound iron, increased by ineffective erythropoiesis, transfusion, or upregulated iron absorption, determine tissue damage. Understanding this biology in a specific disease setting guides management. Coates reviews iron overload in transfusion-dependent hemoglobinopathies; Angelucci contributes insights on treating iron overload before, during, and after stem cell transplantation through discussion of 5 cases; and Leitch and Buckstein share their wisdom on treating iron overload in patients with myelodysplastic syndromes, outlining their approach in several common clinical scenarios.

It has long been recognized that iron overload is toxic and that diagnosis and management of iron overload in patients with hematological disorders are complex and can be disease-specific. Associate Editor Thomas D. Coates presents a series that aims to deconvolute iron overload and provide advice on management. An overarching theme is that the magnitude and duration of exposure to reactive non–transferrin-bound iron, increased by ineffective erythropoiesis, transfusion, or upregulated iron absorption, determine tissue damage. Understanding this biology in a specific disease setting guides management. Coates reviews iron overload in transfusion-dependent hemoglobinopathies; Angelucci contributes insights on treating iron overload before, during, and after stem cell transplantation through discussion of 5 cases; and Leitch and Buckstein share their wisdom on treating iron overload in patients with myelodysplastic syndromes, outlining their approach in several common clinical scenarios.

Some antibodies that drive autoimmune hemolytic anemia do so by activating complement, including immunoglobulin M antibodies causing cold agglutinin disease (CAD) and some immunoglobulin G subclasses causing warm autoimmune hemolytic anemia (wAIHA). Roman and colleagues report the results of PLAUDIT, a phase 2 study of pegcetacoplan, a C3 complement inhibitor, in primary CAD and wAIHA. The authors found that by 8 weeks and over 48 weeks, hemolysis was reduced, hemoglobin levels increased, fatigue scores improved, and that the drug was well tolerated. Pegcetacoplan may represent an effective therapy for CAD in selected patients with wAIHA, and a phase 3 trial is ongoing.

Venetoclax and azacitidine (Ven-Aza) are used as a standard first-line therapy for older patients with acute myeloid leukemia (AML), inducing remission in approximately two-thirds of cases. Ven-Aza has efficacy in some patients with relapsed AML, but selecting patients who are most likely to respond is difficult. Kytölä et al report on the prospective phase 2 VenEx trial, which addresses this question, and the authors demonstrate utility for ex vivo venetoclax sensitivity testing to accurately predict individual response and overall survival with Ven-Aza. The rapid turnaround assay is likely to assist in therapy selection for relapsed or untreated secondary AML.

IKZF1, a zinc finger transcription factor, regulates differentiation, proliferation, and survival of lymphoid cells; however, how it modifies chromatin accessibility to activate or repress gene expression has been a puzzle. Utilizing quantitative and time-sensitive analyses, Zhang et al reveal that IKZF1 predominantly interacts with corepressors to mediate transcriptional silencing through a rapid loss of chromatin accessibility and reduced levels of H3 lysine 27 acetylation, especially at enhancers. These data refine thinking about IKZF1’s role as a switch that determines lymphocyte fate.

Factor XIII (FXIII) is activated by thrombin in the last step of the coagulation cascade, cross-linking fibrin and determining clot stability, composition, and size. Inactive FXIII is a heterotetramer of 2 catalytic A subunits and regulatory B subunits. For the first time, Singh and colleagues report on a 2.4 Å resolution cryogenic electron microscopy (cryo-EM) structure of the heterotetramer. This visualization advances basic knowledge, enables better interpretation of how molecular defects cause bleeding phenotypes, and offers guidance for the design of novel therapeutic strategies.