Blood
Articles in this Issue
Prognostic impact of variant allele frequency in intensively treated patients with NPM1-mutated AML: a PETHEMA study
NPM1-mutated acute myeloid leukemia (AML) is genetically well-defined, but clinical outcomes remain heterogeneous, suggesting that quantitative clonal features may refine current risk stratification....
Five-year survival outcomes from TRANSCEND NHL 001 of lisocabtagene maraleucel in R/R LBCL
We present 5-year survival results in patients with R/R LBCL from TRANSCEND NHL 001 (TRANSCEND), including data from the separate long-term follow-up (LTFU) study. Overall, 345 patients were leukapher...
GLUL pitches in thrombocytopoiesis by restricting ammonia accumulation during megakaryocyte maturation
Polyploidization resulted from massive DNA synthesis is crucial for megakaryocyte maturation, while the regulatory mechanisms of cell fitness upon this special cellular process remain poorly understoo...
PKMYT1 is a Targetable Vulnerability in del(17p) High-Risk Multiple Myeloma
Deletion of 17p is among the most adverse cytogenetic abnormalities in multiple myeloma (MM). By integrating RNA-seq data from patient MM cells with genetic dependency data from MM cell lines, we iden...
Histidine‑rich Glycoprotein Modulates Platelet Adhesion and Aggregation by Binding to GPIbα and GPIIb/IIIa
Histidine-rich glycoprotein (HRG) is a 75-kDa plasma protein produced by the liver and circulating at about 2 µM, with an additional pool in platelets that is released upon activation. Previously, we...
Therapeutic Targeting of IL-17A-Driven PTGS2/NLRP3 Inflammasome Activation in Juvenile Myelomonocytic Leukemia
Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric myelodysplastic syndrome or myeloproliferative disorder for which hematopoietic stem cell transplantation remains the only curative o...
Type I interferon-activated NK cells control polycythemia vera in vivo
Polycythemia vera (PV) is a clonal hematopoietic stem cell (HSC) disorder resulting in overproduction of erythrocytes. While Interferon-a (IFN-a) has shown therapeutic efficacy in PV and other myelopr...
Long-term stability of posttranscriptional genetic silencing of BCL11A using a shmiR vector in Sickle Cell Disease
Sickle cell disease (SCD) is characterized by chronic hemolysis, painful vaso-occlusive episodes (VOE) and end organ damage. High levels of fetal hemoglobin (HbF) attenuate the disease phenotype. We u...
Arlocabtagene autoleucel-a GPRC5D-targeted CAR T-cell therapy in heavily pretreated relapsed/refractory multiple myeloma
Patients with relapsed/refractory multiple myeloma (RRMM) have limited treatment options. Arlocabtagene autoleucel (arlo-cel, BMS-986393) is an autologous chimeric antigen receptor (CAR) T-cell therap...
Ziftomenib with venetoclax and azacitidine in relapsed/refractory NPM1-mutated acute myeloid leukemia
Ziftomenib - a potent, selective, oral menin inhibitor - is approved as monotherapy for adults with relapsed/refractory (R/R) NPM1-mutated acute myeloid leukemia (NPM1-m AML). The KOMET-007 phase 1 tr...
[211At]Astatine-Based Conditioning with a Humanized CD45 Antibody for Autologous Hematopoietic Stem Cell Gene Therapy
Successful transplantation of autologous gene-modified hematopoietic stem/progenitor cells (HSPCs) requires efficient ablation of resident hematopoietic stem cells. Since conventional myeloablative co...
The red blood cell proteome and interactome identify a Band 3-BLVRB axis regulating hypoxic metabolic adaptation
Red blood cells (RBCs) are transcriptionally silent yet dynamically remodel metabolism in response to oxygen tension. Using ultra-pure human RBCs, we generated the deepest contamination-free proteome...
Dynamic genetic and nongenetic RAS pathway activation drives resistance to FLT3 and BCL2 inhibitor therapy
Bulk sequencing of relapsed tumors reveals mutations associated with resistance to cancer therapy but is insufficient to fully assess all causes of relapse. Due to inherent tumor heterogeneity, on-tre...
Reduced platelet formation associated with serine metabolic dysregulation in integrin αIIbβ3-deficient megakaryocytes
Glanzmann Thrombasthenia (GT) is characterized by absent platelet aggregation in response to all agonists except ristocetin and is caused by recessive inactivating variants in ITGA2B or ITGB3. While G...
The fetal specific gene LIN28B is essential for human fetal B-lymphopoiesis and initiation of KMT2A::AFF1 infant leukemia
Infant ALL (iALL) is initiated in utero, most often by rearrangement of the KMT2A gene (KMT2Ar). It carries a very poor prognosis despite a lack of additional oncogenic driver mutations common in chil...
DOT1L Shapes ncPRC1-Target Gene Repression to Maintain Germinal Center B Cell Identity of Diffuse Large B cell Lymphoma
Germinal center (GC) B cell-like diffuse large B cell lymphoma (GCB-DLBCL) depends on the cooperative activity of the histone methyltransferases DOT1L and EZH2 to maintain its pro-proliferative GCB ce...
IL-16 production is a mechanism of resistance to BTK inhibitors and R-CHOP in lymphomas
Resistance to Bruton tyrosine kinase (BTK) inhibitors remains a major clinical challenge in B-cell lymphomas and often occurs in the absence of BTK or PLCG2 mutations. Here, we investigated non-geneti...
Chromosome 5q deletion drives evolution of aneuploidy in myeloid neoplasms with complex karyotype
Clonal acquisition of multiple chromosomal abnormalities in hematopoietic stem and progenitor cells (HSPCs) is a hallmark of high-risk acute myeloid leukemias with complex karyotype (AML-CK). AML-CK i...
Venetoclax Plus Pediatric Regimen in Adolescents and Adults with Ph-Negative Acute Lymphoblastic Leukemia
The BCL-2 inhibitor venetoclax has shown promise in acute lymphoblastic leukemia (ALL), but its role in first-line therapy for newly diagnosed (ND) Philadelphia chromosome-negative (Ph⁻) ALL is undefi...
N6-methyladenosine reader IGF2BP2 in T-cell lymphoma
Peripheral T-cell lymphoma (PTCL) represents a highly heterogeneous and aggressive lymphoid neoplasm, lacking pathogenic biomarkers of RNA modification with therapeutic potential. IGF2BP2 is recognize...
No overall increased risk of death in individuals with sickle cell trait: a study of 467 779 general population adults
Uncertainty remains about whether sickle cell trait (SCT) shortens life or predispose to disease. Therefore, we examined whether SCT-carriers had increased risk of death or diseases linked to SCT. We...
Inhibition of the Atypical Kinase WNK1 as a Therapeutic Strategy in TAL-related T-cell Acute Lymphoblastic Leukemia
Driver mutations in T-cell acute leukemia (T-ALL) rarely affect druggable kinases. However, these kinases can be aberrantly activated or repressed as secondary oncogenic events. Thus, integrating unbi...
TGFβ-PDL1 signaling in neutrophils preserves lung barrier during hyperinflammation
The hyperinflammatory syndromes in critically ill patients, including trauma, sepsis, and acute lung injury, are characterized by dysregulated neutrophil responses that contribute to tissue damage and...
Proteomic profiling identifies systemic drivers of blood-brain barrier injury in sickle cell disease
Sickle cell disease (SCD) causes brain injury and cognitive disability. Systemic inflammation and endothelial injury are central to SCD pathophysiology, yet the relationship between systemic drivers o...
Targeting PRMT9 Overcomes Venetoclax Resistance in AML by Modulating Splicing and Inhibiting Translation
Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) is required for cancer cell proliferation, but whether PRMTs mediate resistance to therapy remains elusive. Here, we have...