MicroRNA Profiling of Bone Marrow Plasma Extracellular Vesicles in Multiple Myeloma, Extramedullary Disease, and Plasma Cell Leukemia.

Multiple myeloma is a plasma cell malignancy characterized by an abnormal increase in monoclonal immunoglobulins. Despite significant advances in treatment, some patients progress to more aggressive forms of multiple myeloma, including extramedullary disease or plasma cell leukemia. Although the exact molecular mechanisms are not known, several studies have confirmed the involvement of small extracellular vesicle-enriched microRNAs in multiple myeloma progression.

Real-World Evidence on Prognostic Value of MRD in Multiple Myeloma Using Flow Cytometry.

Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting.

JAK2V617F mutation and circulating extracellular vesicles in essential thrombocythemia.

The clinical course of essential thrombocythemia (ET) is complicated with thrombosis which significantly impacts patients' mortality. Studies have identified JAK2V617F mutation as an independent risk factor for thrombosis. Circulating extracellular vesicles (EVs) were evaluated in several studies regarding myeloproliferative neoplasms and thrombosis as potential biomarkers.

Involvement of Small Non-Coding RNA and Cell Antigens in Pathogenesis of Extramedullary Multiple Myeloma.

Extramedullary multiple myeloma (EMD) is an aggressive disease; malignant plasma cells lose their dependence in the bone marrow microenvironment and migrate into tissues. EMD is a negative prognostic factor of survival. Using flow cytometry and next-generation sequencing, we aimed to identify antigens and microRNAs (miRNAs) involved in EMD pathogenesis.

The Clinical Significance of Circulating Microparticles Concerning Thrombosis in BCR/ABL1-negative Myeloproliferative Neoplasms.

Background/aim: This work aimed to prospectively evaluate the clinical significance of circulating microparticles (MPs) in relation to thrombotic risk factors and thrombotic complications in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN).

Patients And Methods: In a cohort of 206 patients with MPN, MPs' procoagulant activity was measured by the Zymuphen functional assay in 429 samples, while platelet- and erythrocyte-MPs were enumerated by flow cytometry in 558 samples.

Results: MPN patients had higher MP levels than the control group.

Necessity of flow cytometry assessment of circulating plasma cells and its connection with clinical characteristics of primary and secondary plasma cell leukaemia.

Plasma cell leukaemia (PCL) is a rare and very aggressive plasma cell disorder. Preventing a dismal outcome of PCL requires early diagnosis with appropriate analytical tools. Therefore, the investigation of 33 patients with primary and secondary PCL was done when the quantity of circulating plasma cells (PCs) using flow cytometry (FC) and morphology assessment was evaluated.

Plasmacytoid Dendritic Cells in Patients with MGUS and Multiple Myeloma.

Background: Plasmacytoid dendritic cells (pDCs) play prominent roles in mediating innate and adaptive immune responses. However, it is unclear how pDCs contribute to the immunosuppressive tumor microenvironment described in multiple myeloma (MM).

Methods: Newly diagnosed myeloma patients (MM, = 37) were analyzed to determine the pDC counts in comparison to peripheral blood (PB, = 53) and bone marrow (BM, = 10) samples of age-matched healthy donors (HD) using flow cytometry.

Prognostic significance of lymphocyte patterns in multiple myeloma patients after autologous transplant.

Despite the high efficacy of current induction regimens, most multiple myeloma (MM) patients relapse over time. The link between changes in the immune system and the prognosis of the disease is still not entirely clear. Therefore, we analyzed whether the pattern of bone marrow (BM) lymphocytes during routine BM examination after autologous stem cell transplant (ASCT) is related to disease prognosis or MRD negative complete remission.

The impact of lymphocytosis and CD4/CD8 ratio on the anti-JCV antibody index and clinical data in patients treated with natalizumab.

Background: Natalizumab is an effective therapy in the treatment of relapsing-remitting multiple sclerosis; it induces lymphocytosis (NIL, natalizumab-induced lymphocytosis) and changes the peripheral lymphocyte pattern.

Methods: This study aims to evaluate NIL, peripheral blood lymphocyte subsets, CD4/CD8 ratio, and their impacts on JCV index and clinical data-No Evidence of Disease Activity (NEDA-3) and annualized relapse rate (ARR) in patients treated with natalizumab.

Results: Forty-one patients (33 women) were included in the study.

[Heparin-induced thrombocytopenia: a case report and literature overview].

Heparin-induced thrombocytopenia (HIT) is an immunologically-mediated complication, which usually follows heparin exposition, less frequently exposition to other drugs or even occurs spontaneously. The type of heparin, its dose and mode of application as well as the exposition time, major trauma or operation, and obesity represent the main risk factors for HIT. The probability of HIT correlates with so-called 4T-score.

Dynamics of tumor-specific cfDNA in response to therapy in multiple myeloma patients.

Objectives: Progress in multiple myeloma treatment allows patients to achieve deeper responses, for which the assessment of minimal residual disease (MRD) is critical. Typically, bone marrow samples are used for this purpose; however, this approach is site-limited. Liquid biopsy represents a minimally invasive and more comprehensive technique that is not site-limited, but equally challenging.

[Systemic inflammatory response with high CRP values as the dominant symptom of multiple myeloma].

A man aged 60 years was examined for intense inflammatory response, night sweats, subfebrile and later febrile temperatures and a weight loss of 18 kg in 7 months. CRP was 270 mg / l, i.e.

Whole Exome Sequencing of Aberrant Plasma Cells in a Patient with Multiple Myeloma Minimal Residual Disease.

Multiple myeloma is a plasma cell dyscrasia. It is the second most common hematological malignancy which is characterized by proliferation of clonal plasma cells producing harmful monoclonal immunoglobulin. Despite treatment modalities greatly evolved during the last decade, small amount of aberrant residual cells reside in patients after therapy and can cause relapse of the disease.

Circulating Plasma Cells in Monoclonal Gammopathies.

Background: Monoclonal gammopathies are characterized by presence of clonal plasma cells in the bone marrow, although peripheral blood circulating plasma cells can be found in a significant proportion of patients. The number of circulating plasma cells is an independent prognostic marker associated with shorter survival, but it can also help to predict early relapse. The reason and mechanism of plasma cell expansion from the bone marrow to enter peripheral blood is still not entirely clear, but possible changes in the expression of adhesion molecules are probably involved.

Minimal Residual Disease Assessment in Multiple Myeloma by Multiparametric Flow Cytometry.

Background: Progress in treatment of multiple myeloma extensively increased patient remission rates, so minimal residual disease (MRD) detection becomes essential to assess the effectivity of treatment and depth of complete response. Nowadays, multiparametric flow cytometry (MFC) is the most used method for monitoring of MRD presence in the bone marrow of multiple myeloma patients; however, detection on molecular level can be used as well. It is evident that choice of protocol used for MFC-MRD assessment can significantly affect required results; nevertheless, standardized and highly sensitive approach of "next generation flow" is already available.

Waldenström's macroglobulinemia: Two malignant clones in a monoclonal disease? Molecular background and clinical reflection.

Waldenström's macroglobulinemia (WM) is a complex disease characterized by apparent morphological heterogeneity within the malignant clonal cells representing a continuum of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. At the molecular level, the neoplastic B cell-derived clone has undergone somatic hypermutation, but not isotype switching, and retains the capability of plasmacytic differentiation. Although by classical definition, WM is formed by monoclonal expansion, long-lived clonal B lymphocytes are of heterogeneous origin.

A first Czech analysis of 1887 cases with monoclonal gammopathy of undetermined significance.

Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition with a risk of malignant conversion.

Patients And Methods: With the aim to estimate the cumulative risk MGUS progression to hematologic malignancies, we analyzed a nationwide population-based cohort of 1887 MGUS patients from the Czech Registry of Monoclonal Gammopathies (RMG) between 2007 and 2013.

Results: During the follow-up period (median 4 years; range 0.

Do human B-lymphocytes avoid aging until 60 years?

Broad changes in human innate and adaptive immunity are associated with advanced age. The age-related alteration of gene expression was reported for both T and B lymphocytes. We analysed the genome-wide expression profiles (n=20) of naive and whole B cell populations from young and early aged healthy donors under 60 years.

Activity of aldehyde dehydrogenase in B-cell and plasma cell subsets of monoclonal gammopathy patients and healthy donors.

Background: Aldehyde dehydrogenase (ALDH) is highly active in physiological stem cells as well as in tumor-initiating cells of some malignancies including multiple myeloma (MM). Finding higher activity of ALDH in some cell subsets in monoclonal gammopathies (MG) could identify potential source of myeloma-initiating cells (MICs).

Methods: Bone marrow of 12 MM, 9 monoclonal gammopathy of undetermined significance (MGUS), and 10 healthy donors (HD) were analyzed by flow cytometry.