Identification of four autophagy-related genetic variants as risk factors for chronic lymphocytic leukemia.

We investigated the influence of 55,583 autophagy-related single nucleotide polymorphisms (SNPs) on chronic lymphocytic leukemia (CLL) risk across four independent populations comprising 5,472 CLL cases and 726,465 controls. We also examined their impact on overall survival (OS), time to first treatment (TTFT), autophagy flux, and immune responses. A meta-analysis of the four populations identified, for the first time, significant associations between CDKN2A (rs3731204) and BCL2 (rs4940571, rs12457371, rs1026825) SNPs and CLL risk, with CDKN2A showing the strongest association (p=1.

State of the art biology, progression, and clinical management of monoclonal B-cell lymphocytosis (MBL): consensus report from the Intercepting Blood Cancers Workshop Committee.

In March 2023 and 2024, a panel of international experts convened at the first and second Intercepting Blood Cancers (IBC) Workshops, with the aim of better appreciating the diagnostic challenges, pathophysiology, and potential therapeutic interventions for precursor malignant hematology conditions. Here, we report a summary of the proceedings from the sessions focused on monoclonal B-cell lymphocytosis (MBL)/chronic lymphocytic leukemia (CLL). We highlight four main content areas: biology of MBL, clinical implications of MBL, progression of MBL and transformation from indolent CLL to aggressive disease, and opportunities for therapeutic intervention in early CLL.

NK Alloreactivity Evaluation According to KIR-HLA Interaction Models Influences the Outcome of Haploidentical Haematopoietic Stem-Cell Transplantation Based on Post-Transplant Cyclophosphamide.

Haploidentical haematopoietic stem-cell transplantation (haplo-HSCT) is characterised by a high degree of HLA mismatching. Therefore, NK alloreactivity driven by the interactions between KIR and HLA mismatched molecules could benefit its outcome. However, the influence of NK alloreactivity in haplo-HSCT with post-transplant Cyclophosphamide (PTCy) remains controversial.

Exploring the role of cyclin D1 in the pathogenesis of multiple myeloma beyond cell cycle regulation.

Cyclins D could be a unifying event in multiple myeloma (MM), even though MM is not typically considered a proliferative disease. In this study, we hypothesized that cyclins D might have additional roles in the pathogenesis of MM beyond cell cycle control. We showed that overexpression of CCND1 and CCND2 in MM cell lines lacking these proteins revealed a mutually exclusive expression pattern, with both cyclins D localized in the cytoplasm and no impact on proliferation.

Disease-specific U1 spliceosomal RNA mutations in mature B-cell neoplasms.

Recurrent mutations in the third base of U1 spliceosomal RNA responsible for marked splicing and expression abnormalities have been described in chronic lymphocytic leukemia (CLL) and some solid tumors. However, the clinical significance of these mutations in large and independent CLL cohorts as well as their presence in other B-cell neoplasms is unknown. Here we characterized U1 mutations in 1670 CLL and 363 mature B-cell lymphomas.