High genomic complexity (HGC) is linked to poor prognosis in CLL, but its independent prognostic value remains uncertain amid emerging biomarkers. We analysed copy number alterations (CNA) in 495 untreated patients from (immuno)chemotherapy trials (CLL4, ADMIRE, ARCTIC), incorporating IGHV status, telomere length (TL), targeted sequencing and DNA-methylation subtypes. Patients...
Disease progression, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) are the main causes of failure after allogeneic hematopoietic cell transplantation (SCT) for myeloid neoplasms. T-cell epitope–based models classify HLA-DPB1 mismatches by permissiveness and have been associated with differential risks of GVHD, relapse, and NRM. However, most studies were...
Whether mitigation of myeloproliferation improves prognosis of CMML independently of bone marrow response is unknown. Flow-defined classical monocytes (cMo) and immature granulocytes (iGRAN) have not yet been studied as biomarkers of response. We inspected the prognostic value of WBC, circulating monocytes, cMo and iGRANs in the 120 DACOTA (NCT02214407) patients randomized to...
Many patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) are still less sensitive to tyrosine kinase inhibitors (TKIs). Ph+ ALL shows a high incidence of IKZF1 deletions. Casein kinase II (CK2)-mediated hyperphosphorylation of IKZF1, encoding protein IKAROS, contributes to its dysfunction, and CK2 inhibitor, CX-4945, restores IKAROS function in...
Prefibrotic primary myelofibrosis (prePMF) and essential thrombocythemia (ET) are distinct myeloproliferative neoplasms (MPNs) with overlapping clinical features, often leading to diagnostic uncertainty. We developed an artificial intelligence (AI) framework with human interpretability to distinguish prePMF from ET using digitized hematoxylin and eosin-stained bone marrow biopsy...
Currently there is no established prognostic scoring system for patients with chronic myeloid leukemia (CML) in blast phase (BP). This study aimed to identify prognostic factors of CML-BP in a large cohort of prospectively and retrospectively collected patients and to develop a readily available prognostic scoring system at the onset of BP to enable future comparison between...
Multiple myeloma (MM) resistant to CD38 antibodies, two immunomodulatory drugs (IMiDs), two proteasome inhibitors (PIs), and both BCMA- and GPRC5D-directed immunotherapies defines hepta-refractory MM, a novel end-stage entity. In a multi-center cohort of 37 patients, median overall survival was 12.8 months, with progression-free survival across salvage therapy lines of only 2.7–3...
Acute myeloid leukemia (AML) is an aggressive myeloid malignancy with a poor prognosis. Venetoclax (Ven), a BCL2 inhibitor, has shown promising results but often leads to relapse due to mitochondrial dysregulation, particularly due to upregulation of the anti-apoptotic protein MCL1. Overexpression of the transcription factor STAT3 has been linked to poor survival in AML patients...
Aggressive B-cell lymphomas, driven by MYC overexpression, exhibit rapid progression, resistance to therapies, and poor survival. While chimeric antigen receptor (CAR)-engineered T cells have demonstrated remarkable clinical efficacy in B-cell lymphomas, nearly half of patients who initially respond to CAR-T therapy eventually develop resistance and disease progression. In this...
With increasing survival in acute lymphoblastic leukemia (ALL), long-term toxicities have become a critical aspect. A novel measure, designated Severe Toxicity-free survival (STFS), was developed through international consensus to integrate the most severe, symptomatic organ toxicities in outcome evaluation. This measure has not been applied to real-world data before. We assessed...
Hypoxia-inducible factors (HIFs) are master transcriptional regulators, central to cellular survival in hypoxia and frequently activated within malignancy. Whilst malignant context directs the role of HIFs within oncogenesis, these mechanisms are not well characterised. Applying the JAK2V617F myeloproliferative neoplasms (MPNs) oncogene-driver model, in which HIF-1α is stabilised...
Aberrant activation of NF-κB transcription factors is a hallmark of human lymphomas. Most lymphoma-intrinsic as well as microenvironment-induced NF-κB activation occurs upstream of the key kinase IKK2, therefore affecting additional pathways. Here, we show that canonical NF-κB signaling in mouse B cells, induced through the expression of one or two copies of a constitutively...