Measurement of Immunoglobulin Intraclonal diversification refines the clinical impact of IGHV mutational status in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) cells may bear mutations in IGHV genes, the 2%-cutoff allowing to discriminate two subsets, unmutated (U)- or mutated (M)-CLL, with different clinical course. IGHV genes may also incorporate additional ongoing mutations, a phenomenon known as intraclonal diversification (ID). Here, through an original bioinformatic workflow for NGS data, we used the inverse Simpson Index (iSI) as diversity measure among IGHV sequences to dichotomize cases with different ID levels into ID (iSI ≥ 1.

Familial Forms of Chronic Lymphocytic Leukemia Have a Worse Prognosis Than Sporadic Forms: an Italian Case-Control Study.

Familial chronic lymphocytic leukemia (CLL) constitutes 5-7% of CLL and has previously shown a more aggressive pattern of evolution compared to sporadic CLL, even if no difference in overall survival (OS) has been observed. This multicenter case-control study aimed to compare clinical features, molecular biomarkers, and patient outcomes of familial and sporadic CLL. Adult CLL patients were enrolled from 18 Italian centers, with familial CLL defined as having at least one first-degree relative affected by CLL.

Prognostic relevance of bone marrow immune cell fractions in newly diagnosed B-cell non-Hodgkin lymphoma patients.

Introduction: Non-Hodgkin lymphomas (NHLs) are the most common hematological malignancies worldwide. Among these, B-cell lymphomas (B-NHLs) are the second leading cause of death in hematologic neoplasms.

Material And Methods: In this study, a detailed immunophenotypic analysis of lymphocytes in the bone marrow aspirate (BMA) of 75 patients with four different subtypes of B-NHLs was performed at diagnosis.

The VLA-4 integrin is constitutively active in circulating chronic lymphocytic leukemia cells via BCR autonomous signaling: a novel anchor-independent mechanism exploiting soluble blood-borne ligands.

In chronic lymphocytic leukemia (CLL), survival of neoplastic cells depends on microenvironmental signals at lymphoid sites where the crosstalk between the integrin VLA-4 (CD49d/CD29), expressed in ~40% of CLL, and the B-cell receptor (BCR) occurs. Here, BCR engagement inside-out activates VLA-4, thus enhancing VLA-4-mediated adhesion of CLL cells, which in turn obtain pro-survival signals from the surrounding microenvironment. We report that the BCR is also able to effectively inside-out activate the VLA-4 integrin in circulating CD49d-expressing CLL cells through an autonomous antigen-independent BCR signaling.

NFKBIE mutations are selected by the tumor microenvironment and contribute to immune escape in chronic lymphocytic leukemia.

Loss-of-function mutations in NFKBIE, which encodes for the NF-κB inhibitor IκBε, are frequent in chronic lymphocytic leukemia (CLL) and certain other B-cell malignancies and have been associated with accelerated disease progression and inferior responses to chemotherapy. Using in vitro and in vivo murine models and primary patient samples, we now show that NFKBIE-mutated CLL cells are selected by microenvironmental signals that activate the NF-κB pathway and induce alterations within the tumor microenvironment that can allow for immune escape, including expansion of CD8+ T-cells with an exhausted phenotype and increased PD-L1 expression on the malignant B-cells. Consistent with the latter observations, we find increased expression of exhaustion markers on T-cells from patients with NFKBIE-mutated CLL.

Measurable residual disease in chronic lymphocytic leukemia.

Measurable residual disease (MRD) is defined as the presence of residual cancer cells after treatment in patients with clinically undetectable disease, who would otherwise be considered in complete remission. It is a highly sensitive parameter which indicates the disease burden and predicts survival in this setting of patients. In recent years, MRD has gained a role in many hematological malignancies as a surrogate endpoint for clinical trials: undetectable MRD has been correlated to longer progression free survival (PFS) and overall survival (OS).

Case report: Hematologic malignancies concomitant diagnosis of hairy cell leukemia and chronic lymphocytic leukemia: A rare association.

A case of concomitant hairy cell leukemia (HCL) and chronic lymphocytic leukemia (CLL) in a 50- year-old man was reported. Flow cytometry and droplet digital PCR (ddPCR) were used to detect the B-Raf proto-oncogene (BRAF) V600E mutation. The HCL population was the predominant component.

Potential Mechanisms by which Glucocorticoids Induce Breast Carcinogenesis through Nrf2 Inhibition.

Breast cancer is the most common malignancy among women worldwide. Several studies indicate that, in addition to established risk factors for breast cancer, other factors such as cortisol release related to psychological stress and drug treatment with high levels of glucocorticoids may also contribute significantly to the initiation of breast cancer. There are several possible mechanisms by which glucocorticoids might promote neoplastic transformation of breast tissue.

Flow cytometric evaluation of measurable residual disease in chronic lymphocytic leukemia: Where do we stand?

Measurable residual disease (MRD) has emerged as a relevant parameter of response to therapy in chronic lymphocytic leukemia (CLL). Although several methods have been developed, flow cytometry has emerged as the most useful and standardized approach to measure and quantify MRD. The improved sensitivity of MRD measurements has been paralleled by the development of more effective therapeutic strategies for CLL, increasing the applicability of MRD detection in this setting.

Subcutaneous immunoglobulins in chronic lymphocytic leukemia with secondary antibody deficiency. A monocentric experience during Covid-19 pandemics.

Secondary antibody deficiency (SAD) is a frequent manifestation of chronic lymphocytic leukemia (CLL) that increases the risk of infections. However, no formal guideline are available regarding the eligibility for prophylaxis or the delivery method, dosage, frequency of administration and duration of immunoglobulin replacement therapy (IgRT). The aim of this study was to assess the efficacy and safety of subcutaneous IgRT (SCIg) and its impact on quality of life (QoL) of CLL pts in the Covid-19 era.

Circulating Regulatory T-Cell Number Does Not Predict Prognosis of Monoclonal Gammopathies of Uncertain Significance.

FOXP3-expressing regulatory T-cells (Tregs), which suppress aberrant immune response against self-antigens, also suppress anti-tumor immune response. It has been shown that there is an increased proportion of Tregs in several different human malignancies, although the actual mechanism remains unclear. The research aims to explore the relationship between the number of Tregs and a predict prognosis in particular hematological diseases as monoclonal gammopathies of uncertain significance (MGUS).

CD200 Baseline Serum Levels Predict Prognosis of Chronic Lymphocytic Leukemia.

Membrane-bound CD200 is overexpressed in chronic lymphocytic leukemia (CLL), and there is some evidence that its soluble ectodomain (sCD200) could also be involved in the pathophysiology and the disease. However, very little is known about sCD200's prognostic significance. sCD200 was tested at diagnosis in 272 patients with CLL and in 78 age- and sex-matched healthy subjects using a specific human CD200 (OX-2 membrane glycoprotein) ELISA kit.

Comparison of cardiovascular disease and cancer prevalence between Mediterranean and north European middle-aged populations (The Cilento on Ageing Outcomes Study and The Malmö Offspring Study).

Mediterranean diet protects from both cardiovascular disease (CVD) and cancer. In the 1960s, Ancel Keys defined the concept of Mediterranean diet in the South Italian region of Cilento and proposed it as a key factor for healthy ageing in the region. The aim of the current study was to compare the prevalence of CVD and cancer between a middle-aged population from Cilento and those of a Northern European population from Malmö, Sweden.

CD200 and Chronic Lymphocytic Leukemia: Biological and Clinical Relevance.

CD200, a transmembrane type Ia glycoprotein belonging to the immunoglobulin protein superfamily, is broadly expressed on a wide variety of cell types, such as B lymphocytes, a subset of T lymphocytes, dendritic cells, endothelial and neuronal cells. It delivers immunosuppressive signals through its receptor CD200R, which is expressed on monocytes/myeloid cells and T lymphocytes. Moreover, interaction of CD200 with CD200R has also been reported to play a role in the regulation of tumor immunity.

-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation.

Chronic lymphocytic leukemia (CLL) is characterized by a low CD20 expression, in part explained by an epigenetic-driven downregulation triggered by mutations of the NOTCH1 gene. In the present study, by taking advantage of a wide and well-characterized CLL cohort (n=537), we demonstrate that CD20 expression is downregulated in SF3B1-mutated CLL in an extent similar to NOTCH1-mutated CLL. In fact, SF3B1-mutated CLL cells show common features with NOTCH1-mutated CLL cells, including a gene expression profile enriched of NOTCH1-related gene sets and elevated expression of the active intracytoplasmic NOTCH1.