Lenka Bešše

Combination of serum microRNA‐320a and microRNA‐320b as a marker for Waldenström macroglobulinemia

IgM monoclonal gammopathies are a group of diseases characterized by increased level of IgM immunoglobulin produced by one clone of B cells. These diseases range trom benign (monoclonal gammopathy ot undetermined significance, MGUS) to malignant, such as Waldenstrom macroglobulinemia (WM) or to a lesser extent multiple myeloma (MM) [1,2]. The criteria that differentiate WM from IgM-MGUS are based on the extent of bone marrow (BM) involvement, amount of serum concentration of the M-proicin, presence or absence of symptomatic disease or more recently, MYD88 (L265P) or CXCR4 mutations [3-6]. Despite that, new criteria for the differential diagnosis between these conditions are still needed, circulating microRNAs (miRNAs) being one of them. Circulating miRNAs are present in different body fluids; they reflect physiological or pathologi cal conditions and can be used tor patient classification [7,8]. Thus, we aimed to investigate the ability of serum miRNAs to distinguish WM from IgM-MGUS as well as IgM-MM patients and healthy donors (HD).

Circulating Serum MicroRNA-130a as a Novel Putative Marker of Extramedullary Myeloma.

Poor outcome of extramedullary disease in multiple myeloma patients and lack of outcome predictors prompt continued search for new markers of the disease. In this report, we show circulating microRNA distinguishing multiple myeloma patients with extramedullary disease from myeloma patients without such manifestation and from healthy donors. MicroRNA-130a was identified by TaqMan Low Density Arrays and verified by quantitative PCR on 144 serum samples (59 multiple myeloma, 55 myeloma with extramedullary disease, 30 healthy donors) in test and validation cohorts as being down-regulated in myeloma patients with extramedullary disease. Circulating microRNA-130a distinguished myeloma patients with extramedullary disease from healthy donors with specificity of 90.0% and sensitivity of 77.1%, patients with extramedullary disease from newly diagnosed multiple myeloma patients with specificity of 77.1% and sensitivity of 34.3% in the test cohort and with specificity of 91.7% and sensitivity of 30.0% in the validation cohort of patients. Circulating microRNA-130a in patients with extramedullary myeloma was associated with bone marrow plasma cells infiltration. Further, microRNA-130a was decreased in bone marrow plasma cells obtained from patients with extramedullary myeloma in comparison to bone marrow plasma cells of myeloma patients without such manifestation, but it was increased in tumor site plasma cells of patients with extramedullary disease compared to bone marrow plasma cells of such patients (p<0.0001). Together, our data suggest connection between lower level of microRNA-130a and extramedullary disease and prompt further work to evaluate this miRNA as a marker of extramedullary disease in multiple myeloma.

Cell-free DNA — Minimally invasive marker of hematological malignancies

Although tumor cells are the most reliable source of tumor DNA, biopsy of the tumor is an invasive procedure that should be avoided in some cases. The main limitation of any biopsy is sampling of one tumor site, which may not represent all malignant clones due to the heterogeneity of the tumor. These clones respond to treatment differently and thus directly influence survival of the patient. Circulating cell‐free DNA (cfDNA) is released from multiple tumor sites, reflects overall heterogeneity of the tumor, and correlates with its progression. Detection of tumor‐specific genetic and epigenetic aberrations in cfDNA could have a direct impact on molecular diagnosis, prognosis, follow‐up of disease, monitoring of minimal residual disease, and response to treatment. While most cfDNA data are still experimental, they are very promising. This review focuses on cfDNA in hematological malignancies.

Cytogenetics in multiple myeloma patients progressing into extramedullary disease

Extramedullary disease in multiple myeloma patients is an uncommon event occurring either at the time of diagnosis, or during disease progression/relapse. This manifestation is frequently associated with poor outcome and resistance to treatment. We evaluated chromosomal alterations of plasma cells of multiple myeloma patients with extramedullary relapse, either in the bone marrow (BM) or at extramedullary sites, and in previous BM collection by interphase fluorescence in situ hybridization.

MicroRNAs in urine are not biomarkers of multiple myeloma

BackgroundIn this study, we aimed to identify microRNA from urine of multiple myeloma patients that could serve as a biomarker for the disease.ResultsAnalysis of urine samples was performed using Serum/Plasma Focus PCR MicroRNA Panel (Exiqon) and verified using individual TaqMan miRNA assays for qPCR. We found 20 deregulated microRNA (p < 0.05); for further validation, we chose 8 of them. Nevertheless, only differences in expression levels of miR-22-3p remained close to statistical significance.ConclusionsOur preliminary results did not confirm urine microRNA as a potential biomarker for multiple myeloma.

Promising activity of nelfinavir-bortezomib-dexamethasone (NeVd) in proteasome inhibitor-refractory multiple myeloma

TO THE EDITOR: Treatment of proteasome inhibitor (PI)–refractory multiple myeloma (MM) is challenging, with response rates of only 15% to 35% being achieved with next-generation drugs such as pomalidomide, carfilzomib, and daratumumab, alone or in combination.[1][1][⇓][2]-[3][3] The oral HIV

Improving the efficacy of proteasome inhibitors in the treatment of renal cell carcinoma by combination with the human immunodeficiency virus (HIV)-protease inhibitors lopinavir or nelfinavir

To assess the potential of second‐generation proteasome inhibition by carfilzomib and its combination with the human immunodeficiency virus (HIV) protease inhibitors (HIV‐PIs) lopinavir and nelfinavir in vitro for improved treatment of clear cell renal cell cancer (ccRCC).