The continuous improvement in progression-free survival (PFS) of multiple myeloma (MM) patients raises interest in evaluating peripheral residual disease (PRD) towards more frequent readouts of tumor kinetics while preserving quality of life. Here we present BloodFlow, a new method that combines immunomagnetic enrichment of CD138+ circulating plasma cells in peripheral blood (PB) with next-generation

The majority of calreticulin (CALR) mutations in myeloproliferative neoplasms (MPNs) are classified as either type 1, a 52 base-pair deletion (CALRdel52), or type 2, a 5 base-pair insertion (CALRins5). Both are gain-of-function (GOF) mutations that generate an identical mutant C-terminal tail, which mediates the binding to and activation of the thrombopoietin receptor MPL. We recently reported that

Suppression of plasminogen activation and/or plasmin activity (PA) reduces blood loss and decreases hemorrhage-related death. However, whether the endogenous PA system is a biological mechanism to prevent intravascular thrombus formation is debated, and the potential that reduced PA may increase venous thrombosis/thromboembolism (VTE) risk cautions against the use of antifibrinolytic agents. We aimed

Early recognition and treatment of heparin-induced thrombocytopenia (HIT) are crucial to prevent severe complications. While immunoassays offer rapid diagnosis, their sensitivity and specificity are suboptimal. Sequential combinations of quantitative immunoassay results improve their diagnostic accuracy. We aimed to validate two Bayesian approaches combining two rapid immunoassays and to compare their

Long noncoding RNAs (lncRNAs) are a significant yet largely uncharted component of the cancer transcriptome, with their isoform-specific functions remaining poorly understood. In this study, we employed RNA-targeting CRISPR-Cas13d to uncover and characterize hundreds of tumor-essential (te)-lncRNA isoforms with clinical relevance. Focusing on multiple myeloma (MM), we targeted the lncRNA transcriptome

The autoimmune response driving hematopoietic stem and progenitor cell (HSPC) destruction in immune-mediated aplastic anemia (AA) remains incompletely understood. We previously identified a disease-specific immune cell network involving T-, B-, and myeloid cells. However, the interactions within this network, the interaction with the microenvironment and the chronological events in AA development,

No standard of care for older patients with aggressive adult T-cell leukemia/lymphoma (ATL) has been established. We evaluated the efficacy of CHOP (cyclophosphamide, doxorubicin, Oncovin [vincristine], and prednisone) every 2 weeks with mogamulizumab (Moga; Moga-CHOP-14) for older patients with untreated ATL. In this multicenter phase 2 trial, patients aged ≥66 years and those aged 56 to 65 years

Transfusion-related acute lung injury (TRALI) is a leading cause of blood transfusion triggered mortality. Recently, we demonstrated the critical role of Fc-dependent complement activation in anti-CD36-mediated murine TRALI. In this study, we found that C5-/- mice were protected and administration of anti-C5 rescued wild-type mice from anti-CD36-mediated TRALI. However, C5aR1-/- mice were not protected

Macrophage activation syndrome (MAS) is believed to be the result of inappropriate proliferation and activation of the mononuclear phagocytic system. Adult-onset Still's disease (AOSD) is characterized by neutrophil activation and a cytokine storm, which can lead to its severe and potentially life-threatening complication MAS. RNA sequencing revealed that neutrophils may play a distinct and enhanced

Although most patients with follicular lymphoma (FL) follow an indolent disease course, some patients experience a critical inflection point when FL transforms into an aggressive lymphoma. Historically, FL transformation (tFL) is marked by poor outcomes, particularly for patients with previous FL-directed treatment. Compared with FL, tFL is marked by numerous additional genetic changes, upregulates

Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell–driven malignancies marked by excessive myelopoiesis and high risk of myelofibrosis, which remains therapeutically challenging. Senescent neutrophils home daily to the bone marrow (BM) to be cleared by macrophages. This avoids their accumulation, which can increase the risk of chronic inflammation or oncogenesis. Neutrophils carrying the

Sepsis is characterized by a systemic inflammation and microvascular thrombosis induced by infection. The nucleotide-oligomerization domain–like receptor family pyrin domain containing 6 protein (NLRP6) possesses both proinflammatory and anti-inflammatory abilities with cell type–specific or tissue-specific functions. However, the role of cell type–specific NLRP6 in sepsis remains poorly understood

As evidenced by the excellent survival outcomes, chronic myeloid leukemia treatment in the era of tyrosine kinase inhibitors (TKIs) is often successful. However, when response milestones are not met or lost, treatment decision-making may be challenging. The availability for first-, second-, or subsequent-line use of 6 different TKIs, each with definite and often nonoverlapping features in terms of

Despite the success of B-cell maturation antigen (BCMA)–targeting chimeric antigen receptor (CAR) T cells (CAR-Ts) in multiple myeloma, patients with high-risk cytogenetic features continue to relapse most quickly and are in urgent need of additional therapeutic options. Here, we identify CD70, widely recognized as a favorable immunotherapy target in other cancers, as a specifically upregulated cell

VEXAS (Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic) syndrome is a severe monogenic disorder caused by somatic UBA1 mutations, characterized by inflammation, cytopenias and frequent association with myelodysplastic neoplasms (MDS). Steroid dependence is common, and targeted therapies have demonstrated limited efficacy. Azacitidine (AZA), a hypomethylating agent used in MDS, has shown potential

Immunotherapy has become standard of care in the treatment of diffuse large B-cell lymphoma (DLBCL). Changes in immunophenotypes observed at first diagnosis predict therapy outcome but little is known about the resolution of these alterations in remission. Comprehensive characterization of immune changes from fresh, peripheral whole blood revealed a functionally relevant increase of myeloid-derived

This study analyzed the genetics of classic Hodgkin lymphoma (cHL) by using circulating tumor DNA (ctDNA). Two genetic subtypes were identified, differing in genetic instability mechanisms: one subtype (64% of cases) showed a higher mutation load and a higher fraction of mutations associated with activation-induced cytidine deaminase and microsatellite instability signatures, whereas the other subtype

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome arising in many contexts. Its underlying mechanisms are often unclear, but defective granule-mediated cytotoxicity (familial HLH) and excess interleukin-18 (IL-18; macrophage activation syndrome) provide clues. Mounting evidence suggests the causes of HLH converge on cytotoxic T lymphocyte (CTL) hyperactivation

Coagulation factor V (FV) is a key protein in maintaining the hemostatic balance, with abnormal plasma levels associated with both thrombotic and hemorrhagic conditions. We propose a comprehensive bioinformatic analysis integrating large-scale proteogenomics and transcriptomic data from original and public data sets. We identify a biological fingerprint of 26 new proteins and loci involved in the regulation

Rare thrombotic events associated with ChAdOx1 nCoV-19 (ChAdOx1) vaccination have raised concerns; however, the underlying mechanisms remain elusive. Here, we report a novel biophysical mechanism by which ChAdOx1 directly interacts with platelets under arterial shear conditions, potentially contributing to postvaccination arterial thrombosis. Using microfluidic post assays, we demonstrate that ChAdOx1

After the introduction of tyrosine kinase inhibitors (TKIs), the number of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic phase chronic myeloid leukemia (CP-CML) has dramatically decreased. Imatinib was the first TKI introduced into the clinical arena, predominantly used in the first-line setting. In cases of insufficient response, resistance, or intolerance

In 2013, we published a perspective entitled, “The myth of the second remission of acute leukemia,” which underscored the dismal outcomes of relapsed acute leukemia in adults. We emphasized that only a few patients achieved second complete remission (CR2) after relapse and were subsequently eligible to receive a potentially curative allogeneic hematopoietic stem cell transplantation (HSCT). Hence,

Insufficient eradication of cancer cells and survival of drug tolerant clones are major relapse driving forces. Underlying molecular mechanisms comprise activated pro-survival and anti-apoptotic signaling leading to insufficient apoptosis and drug resistance. The identification of programmed cell death pathways alternative to apoptosis opens up for possibilities to antagonize apoptosis escape routes

We carried out a single-cell multiomic analysis on a series of MYD88-mutated Waldenström macroglobulinemia (WM) patients and identified 2 distinct subtypes of disease, memory B-cell (MBC)–like and plasma cell (PC)–like, based on their expression of key lineage defining genes. Biologically, the subtypes are characterized by their variable capacity to differentiate fully toward a PC and exhibit unique

Graft-versus-host disease (GVHD) ensues as the most common nonrelapse complication after allogeneic hematopoietic cell transplantation (allo-HCT). A pivotal goal in GVHD management revolves around quelling inflammation. Phagocytic clearance of inflammatory cells contributes substantially to termination of inflammatory processes. Nevertheless, the precise functions of phagocytosis in GVHD remain largely

The prognosis for relapsed or refractory (R/R) nucleophosmin 1–mutated (NPM1m) acute myeloid leukemia (AML) is poor and represents an urgent unmet medical need. Revumenib, a potent, selective menin inhibitor, was recently approved for the treatment of R/R acute leukemia with a KMT2A translocation in patients aged ≥1 year based on results from the phase 1/2 AUGMENT-101 study. Here, we present results

Small molecules that inhibit LSD1 (lysine-specific demethylase 1, KDM1A) have been shown to induce abundant fetal hemoglobin (HbF) levels in red blood cells both in vitro and in vivo, therefore potentially serving as potent and cost-effective therapeutics to treat the β-globinopathies, sickle cell disease (SCD), and β-thalassemia major (TM). However, most LSD1 inhibitors (LSD1is) that induce HbF in

The Jak2 V617F mutation stands as the main driver of myeloproliferative neoplasms (MPNs) by constitutively activating signaling through several type I cytokine receptors, namely erythropoietin, thrombopoietin receptor (TpoR), and granulocyte colony-stimulating factor receptor. Among these, TpoR assumes a pivotal role in hematopoietic stem cell renewal and differentiation, being positioned as a key

We found that 8 of 10 patients with aplastic anemia experienced resolution of platelet transfusion refractoriness following daratumumab administration. Notably, 4 responders achieved hematopoietic recovery, including 3 participants who showed improvements in multilineage blood cell counts, even with daratumumab monotherapy. This trial was registered at www.clinicaltrials.gov as #NCT05832216.

We report 8 patients with ankyrin repeat domain 26 (ANKRD26)–related thrombocytopenia 2 (ANKRD26-RT) with elevated bone marrow myeloblasts and dysmegakaryopoiesis, without somatic genetic abnormalities or progression to malignancy during long-term observation, findings which may constitute inherent ANKRD26-RT biology rather than progression to myeloid malignancy.

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT). Palifermin, a recombinant N-truncated keratinocyte growth factor (KGF), protects epithelial tissues, including the thymus and gut. Although high-dose KGF prevents GVHD in preclinical models, lower doses of palifermin were ineffective in humans. We conducted a phase 1/2 trial evaluating high-dose