Issue Archive

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin B-cell lymphoma that defies cures in most patients. Over the last decade, significant advances have been made in our understanding of the biology of the disease, patient risk stratification, and novel therapies. Associate Editor Philippe Armand presents a series of reviews that provide advice on management of patients, illuminate current understanding of the molecular landscape associated with the disease, and how that may shape future research and care. Ryan et al review the current frontline management of MCL in a rapidly evolving field, underscoring ongoing phase 3 trials; Silkenstedt and Dreyling highlight the emerging treatments for relapsed and refractory MCL; Jain and Wang tackle the critical issue of risk assignment based on clinical and molecular features; and Sarkozy and colleagues explore in depth the biology of MCL with an emphasis not only on intrinsic vulnerabilities but also on the tumor microenvironment.

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin B-cell lymphoma that defies cures in most patients. Over the last decade, significant advances have been made in our understanding of the biology of the disease, patient risk stratification, and novel therapies. Associate Editor Philippe Armand presents a series of reviews that provide advice on management of patients, illuminate current understanding of the molecular landscape associated with the disease, and how that may shape future research and care. Ryan et al review the current frontline management of MCL in a rapidly evolving field, underscoring ongoing phase 3 trials; Silkenstedt and Dreyling highlight the emerging treatments for relapsed and refractory MCL; Jain and Wang tackle the critical issue of risk assignment based on clinical and molecular features; and Sarkozy and colleagues explore in depth the biology of MCL with an emphasis not only on intrinsic vulnerabilities but also on the tumor microenvironment.

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin B-cell lymphoma that defies cures in most patients. Over the last decade, significant advances have been made in our understanding of the biology of the disease, patient risk stratification, and novel therapies. Associate Editor Philippe Armand presents a series of reviews that provide advice on management of patients, illuminate current understanding of the molecular landscape associated with the disease, and how that may shape future research and care. Ryan et al review the current frontline management of MCL in a rapidly evolving field, underscoring ongoing phase 3 trials; Silkenstedt and Dreyling highlight the emerging treatments for relapsed and refractory MCL; Jain and Wang tackle the critical issue of risk assignment based on clinical and molecular features; and Sarkozy and colleagues explore in depth the biology of MCL with an emphasis not only on intrinsic vulnerabilities but also on the tumor microenvironment.

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin B-cell lymphoma that defies cures in most patients. Over the last decade, significant advances have been made in our understanding of the biology of the disease, patient risk stratification, and novel therapies. Associate Editor Philippe Armand presents a series of reviews that provide advice on management of patients, illuminate current understanding of the molecular landscape associated with the disease, and how that may shape future research and care. Ryan et al review the current frontline management of MCL in a rapidly evolving field, underscoring ongoing phase 3 trials; Silkenstedt and Dreyling highlight the emerging treatments for relapsed and refractory MCL; Jain and Wang tackle the critical issue of risk assignment based on clinical and molecular features; and Sarkozy and colleagues explore in depth the biology of MCL with an emphasis not only on intrinsic vulnerabilities but also on the tumor microenvironment.

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin B-cell lymphoma that defies cures in most patients. Over the last decade, significant advances have been made in our understanding of the biology of the disease, patient risk stratification, and novel therapies. Associate Editor Philippe Armand presents a series of reviews that provide advice on management of patients, illuminate current understanding of the molecular landscape associated with the disease, and how that may shape future research and care. Ryan et al review the current frontline management of MCL in a rapidly evolving field, underscoring ongoing phase 3 trials; Silkenstedt and Dreyling highlight the emerging treatments for relapsed and refractory MCL; Jain and Wang tackle the critical issue of risk assignment based on clinical and molecular features; and Sarkozy and colleagues explore in depth the biology of MCL with an emphasis not only on intrinsic vulnerabilities but also on the tumor microenvironment.

In relapsed/refractory follicular lymphoma (R/R FL), achieving remission is not sufficient, as the main challenge is maintaining long-term response without significant toxicity. Sehn and colleagues report the long-term follow-up (3 years) of fixed duration therapy with mosunetuzumab, a bispecific antibody that engages T cells and lymphoma cells, in a phase 1/2 study in patients with R/R FL, finding that the majority of complete responses are maintained beyond 2 years and that normal B-cell recovery occurs after a median of 18 months. With few late toxicities observed, these data support the use of mosunetuzumab as a safe and effective treatment for R/R FL.

Chimeric antigen receptor (CAR) T-cell therapy for acute myeloid leukemia (AML) is confounded by antigen heterogeneity and antigen escape. Silva et al report the development of a novel dual-targeting CAR-T that engages CD70 and secretes a bispecific antibody that not only targets CD33 but also recruits bystander T cells to attack CD33⁺ AML cells. Using in vitro and in vivo models, the authors show increased cytotoxicity, improved tumor control, and increased persistence of these cells, justifying further research to assess efficacy in patients and potential immune-related toxicities and other off-target effects.

The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax is highly active against multiple myeloma (MM) with the t(11;14) translocation; however, some patients develop drug resistance, leading to relapse. Nair et al report that heme plays a critical role in the sensitivity of MM cells to venetoclax, showing that increased heme promotes resistance while inhibition of heme biosynthesis increases sensitivity and that this is driven by activation of MEK-ERK signaling and increased purine biosynthesis. The study uncovers a novel metabolic vulnerability in MM cells that can be potentially targeted, amplifying the effects of BCL2 inhibition.

Bromodomain and extraterminal (BET) bromodomain-containing protein 4 (BRD4) is a therapeutic target in acute myeloid leukemia (AML), but inhibitors show only modest clinical success due to toxicity and resistance when used as monotherapy. Analyzing the epigenomic effect of BRD4/BET inhibition, Shah et al identified a compensatory prosurvival transcriptional feedback loop led by the lysine acetyltransferase coactivator protein p300 that enables tolerance to BET inhibition by suppressing expression of genes critical for AML maintenance. Utilizing both cellular and animal models, the investigators demonstrated that dual inhibition of BET and p300 disrupts this compensatory feedback, specifically when sequential dosing is employed, and suggest this combinatorial approach for future clinical trials.

During storage in blood banks, red blood cells (RBCs) accumulate oxidative damage that make them more susceptible to hemolysis, leading to poor transfusion outcomes. With a comprehensive genetic and metabolic approach, using well-phenotyped mice and human cohorts, D’Alessandro and colleagues provide new insights into the mechanism of RBC “storage lesions.” The authors identify a ferroptosis-like process modulated by Steap3 as a mechanism of red cell damage and provide a potential platform for pharmacological intervention.