Molecular Composition and Kinetics of B Cells During Ibrutinib Treatment in Patients with Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B cells due to constitutive B-cell receptor (BCR) signaling, leading to apoptosis resistance and increased proliferation. This study evaluates the effects of the Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib on the molecular composition, clonality, and kinetics of B cells during treatment in CLL patients. Employing a multi-omics approach of up to 3.

Multilevel Analysis of MYC and BCL2 Aberrations in Diffuse Large B-Cell Lymphoma: Identifying a High-Risk Patient Subgroup Across Cell-of-Origin Using Targeted Sequencing.

Introduction: Diffuse large B-cell lymphoma (DLBCL) exhibits striking clinical and biological heterogeneity. Recent studies have identified new subgroups within germinal center B-cell like (GCB) DLBCL, associated with inferior prognosis, irrespective of MYC and BCL2 translocations. We explored the existence of such a DLBCL high-risk subgroup, based on multilevel aberrations, especially focusing on MYC and BCL2.

SWIGH-SCORE: A translational light-weight approach in computational detection of rearranged immunoglobulin heavy chain to be used in monoclonal lymphoproliferative disorders.

We present a lightweight tool for clonotyping and measurable residual disease (MRD) assessment in monoclonal lymphoproliferative disorders. It is a translational method that enables computational detection of rearranged immunoglobulin heavy chain gene sequences.•The clonotyping tool emphasizes parallelization and applicability across sequencing platforms.

The potential of 3rd-generation nanopore sequencing for B-cell clonotyping in lymphoproliferative disorders.

Lymphoid malignancies are characterized by clonal cell expansion, often identifiable by unique immunoglobulin rearrangements. Heavy (IGH) and light-chain gene usage offers diagnostic insights and enables sensitive residual disease detection via next-generation sequencing. With its adaptable throughput and variable read lengths, Oxford Nanopore thirdgeneration sequencing now holds promise for clonotyping.

Toward Cytogenomics: Technical Assessment of Long-Read Nanopore Whole-Genome Sequencing for Detecting Large Chromosomal Alterations in Mantle Cell Lymphoma.

The current advances and success of next-generation sequencing hold the potential for the transition of cancer cytogenetics toward comprehensive cytogenomics. However, the conventional use of short reads impedes the resolution of chromosomal aberrations. Thus, this study evaluated the detection and reproducibility of extensive copy number alterations and chromosomal translocations using long-read Oxford Nanopore Technologies whole-genome sequencing compared with short-read Illumina sequencing.

Cell-free DNA for detection of clonal B cells in diffuse large B cell lymphoma by sequencing.

Introduction: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma in the western world. It is highly heterogeneous with a variable clinical course, but curable with chemo-immunotherapy in up to 70% of all cases. The lymphoma presents in lymph nodes and/or extranodal lymphoid tissue, and the diagnosis is based on invasive procedures for histopathologic evaluation.

A reference-area-free strain mapping method using precession electron diffraction data.

In this work, we developed a method using precession electron diffraction data to map the residual elastic strain at the nano-scale. The diffraction pattern of each pixel was first collected and denoised. Template matching was then applied using the center spot as the mask to identify the positions of the diffraction disks.

Reproducibility of low-level residual myeloma immunoglobulin detection using ultra-deep sequencing.

Multiple myeloma, a mature B-cell neoplasm, is the second most common hematologic malignancy. Despite advancements in treatment, the disease remains incurable, with more than 100,000 annual deaths worldwide. As recommended by the International Myeloma Working Group, measurable residual disease (MRD) should be addressed at a 10 sensitivity level or beyond for practical purposes.

Exploration of residual disease in stem cell products from mantle cell lymphoma using next-generation sequencing.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become a treatment option for fit patients with mantle cell lymphoma (MCL). However, these patients often relapse within few years, potentially caused by contaminating lymphoma cells within the reinfused stem cell product (SCP). Studies have shown that measurable residual disease, also termed minimal residual disease (MRD), following ASCT predicts shorter survival.

Mantle cell lymphoma and the evidence of an immature lymphoid component.

Mantle cell lymphoma (MCL) is a rare B cell malignancy. The classical MCL subtype is positive for translocation t(11;14), SOX11 expression, and characterized as a mature B cell neoplasm. While it is evident that differentiated B lymphocytes comprise the principal constituent of this malignancy, the possibility of an immature component involving immature progenitor, precursor, or even multipotent stem cells exists.

Acute myeloid leukemia exhibiting clonal instability during treatment: Implications for measurable residual disease assessments.

Next-generation sequencing (NGS) is an excellent methodology for measuring residual disease in acute myeloid leukemia and surveying several subclones simultaneously. There is little experience with interpretation of differential clonal responses to therapy. We hypothesized that differential clonal response could best be studied in patients with residual disease at the time of response evaluation.

Clonal evolution in patients developing therapy-related myeloid neoplasms following autologous stem cell transplantation.

Clonal hematopoiesis (CH) denotes somatic mutations in genes related to myeloid neoplasms present at any variant allele frequency (VAF). Clonal hematopoiesis is associated with increasing age and with a factor 6 increase in the risk of developing therapy-related myeloid neoplasms (tMNs) following autologous stem cell transplantation (ASCT). However, the impact of specific mutations on progression from CH to tMN has yet to be unraveled, and it remains unclear whether mutations directly impact or even drive the development of tMN.

Replicate whole-genome next-generation sequencing data derived from Caucasian donor saliva samples.

Next-generation sequencing (NGS) of whole genomes has become more accessible to biomedical researchers as the sequencing price continues to drop, and more laboratories have NGS facilities or have access to a core facility. However, the rapid and robust development of practical bioinformatics pipelines partly depends on convenient access to data for the testing of algorithms. Publicly available data sets constitute a part of this strategy.

Distal chromosome 1q aberrations and initial response to ibrutinib in central nervous system relapsed mantle cell lymphoma.

Relapse involving the central nervous system (CNS) is an infrequent event in the progression of mantle cell lymphoma (MCL) with an incidence of approximately four percent. We report four cases of MCL with CNS relapse. In three of the four patients a large chromosomal copy-number alteration (CNA) of 1q was demonstrated together with TP53 mutation/deletion.

Perspective: sensitive detection of residual lymphoproliferative disease by NGS and clonal rearrangements-how low can you go?

Malignant lymphoproliferative disorders collectively constitute a large fraction of the hematological cancers, ranging from indolent to highly aggressive neoplasms. Being a diagnostically important hallmark, clonal gene rearrangements of the immunoglobulins enable the detection of residual disease in the clinical course of patients down to a minute fraction of malignant cells. The introduction of next-generation sequencing (NGS) has provided unprecedented assay specificity, with a sensitivity matching that of polymerase chain reaction-based measurable residual disease (MRD) detection down to the 10 level.

Molecular characterization of sorted malignant B cells from patients clinically identified with mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a tumor with a poor prognosis. A few studies have examined the molecular landscape by next-generation sequencing and provided valuable insights into recurrent lesions driving this heterogeneous cancer. However, none has attempted to cross-link the individual genomic and transcriptomic profiles in sorted MCL cells to perform individual molecular characterizations of the lymphomas.