Comparative analyses of DNA extraction methods for whole blood quantification of HCMV DNAemia in patients with hematological diseases: false negative cases in manual method.

Human cytomegalovirus (HCMV) DNA quantitation in whole blood (WB) by real-time or quantitative polymerase chain reaction (qPCR) is a highly sensitive and reproducible diagnostic procedure for monitoring HCMV DNAemia (DNAemia is the detection of DNA in samples of plasma, whole blood, isolated peripheral blood leukocytes or in buffy-coat specimens) in patients. We provided a comparative analysis of HCMV DNA extraction performance by two different techniques, one performed by an automated extractor and the other by a manual method. We observed that the automated extraction method allowed HCMV DNA detection in the presence of weak viremia while no differences are observed when the viral load is greater.

Role of IL-6/STAT3 Axis in Resistance to Cisplatin in Gastric Cancers.

Gastric cancer, the second most common cause of death worldwide, is characterized by poor prognosis and low responsiveness to chemotherapy. Indeed, multidrug resistance, based mainly on cellular and molecular factors, remains one of the most limiting factors of the current approach to gastric cancer (GC) therapy. We employed a comprehensive gene expression analysis through data mining of publicly available databases to assess the role of the signal transducer and activator of transcription 3 (STAT3) in gastric cancer drug efficiency.

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.

Superiority of Droplet Digital PCR Over Real-Time Quantitative PCR for Allele Mutational Burden Assessment in Myeloproliferative Neoplasms: A Retrospective Study.

mutational status is an essential diagnostic index in myeloproliferative neoplasms (MPNs). Although widely used for detection of mutation in peripheral blood (PB), sensitive real-time quantitative PCR (qPCR) presents some methodological limitations. Recently, emerging alternative technologies, like digital droplet PCR (ddPCR), have been reported to overcome some of qPCR's technical drawbacks.

A case of acute promyelocytic leukemia variant with derivative chromosome 3 der(3)t(3;8) associated with 8q partial gain.

Background: Acute promyelocytic leukemia (APL) is characterized by fusion of PML/RARα genes as a result of t(15;17)(q24;q21). APL is now one of the curable hematological malignancies thanks to molecularly targeted therapies based on all-trans retinoic acid (ATRA) and arsenic trioxide (ATX). Extramedullary (EM) relapse is a rare event in APL, ear involvement being even more infrequent, with only six cases so far described.

An update on biology, diagnosis and treatment of primary plasma cell leukemia.

Primary plasma cell leukemia (PPCL) is one of the most aggressive hematological malignancies. The prognosis of PPCL patients remains poor, although some improvements have been made in recent years. Areas covered: In this review recent clinical and biological advances in PPCL are reported.

Knockdown of miR-128a induces Lin28a expression and reverts myeloid differentiation blockage in acute myeloid leukemia.

Lin28A is a highly conserved RNA-binding protein that concurs to control the balance between stemness and differentiation in several tissue lineages. Here, we report the role of miR-128a/Lin28A axis in blocking cell differentiation in acute myeloid leukemia (AML), a genetically heterogeneous disease characterized by abnormally controlled proliferation of myeloid progenitor cells accompanied by partial or total inability to undergo terminal differentiation. First, we found Lin28A underexpressed in blast cells from AML patients and AML cell lines as compared with CD34+ normal precursors.

Abnormal cell-clearance and accumulation of autophagic vesicles in lymphocytes from patients affected with Ataxia-Teleangiectasia.

Ataxia-Teleangiectasia (A-T) is a neurodegenerative disorder due to mutations in ATM gene. ATM in the nucleus ensures DNA repair, while its role in the cytosol is still poorly clarified. Abnormal autophagy has been documented in other neurodegenerative disorders, thus we evaluated whether alteration in this process may be involved in the pathogenesis of A-T by analyzing the autophagic vesicles and the genes implicated in the different stages of autophagy.

Inverse regulation of bridging integrator 1 and BCR-ABL1 in chronic myeloid leukemia.

Endocytosis is the major regulator process of tyrosine kinase receptor (RTK) functional activities. Bridging integrator 1 (BIN1) is a key protein involved in RTK intracellular trafficking. Here, we report, by studying 34 patients with chronic myeloid leukemia (CML) at diagnosis, that BIN1 gene is downregulated in CML as compared to healthy controls, suggesting an altered endocytosis of RTKs.

Myelodysplastic disorders carrying both isolated del(5q) and JAK2(V617F) mutation: concise review, with focus on lenalidomide therapy.

The concomitant presence of del(5q) and JAK2(V617F) mutation is an infrequent event which occurs in rare patients with peculiar cytogenetic, molecular, morphological and clinical features, resembling those of both myelodysplastic syndromes and myeloproliferative neoplasms. Lenalidomide may induce rapid, profound, and long-lasting responses in a subset of these patients. However, the mechanism(s) by which the drug acts in these conditions remain not completely elucidated.

Molecular evidence for a thymus-independent partial T cell development in a FOXN1-/- athymic human fetus.

The thymus is the primary organ able to support T cell ontogeny, abrogated in FOXN1(-/-) human athymia. Although evidence indicates that in animal models T lymphocytes may differentiate at extrathymic sites, whether this process is really thymus-independent has still to be clarified. In an athymic FOXN1(-/-) fetus, in which we previously described a total blockage of CD4(+) and partial blockage of CD8(+) cell development, we investigated whether intestine could play a role as extrathymic site of T-lymphopoiesis in humans.

Human skin-derived keratinocytes and fibroblasts co-cultured on 3D poly ε-caprolactone scaffold support in vitro HSC differentiation into T-lineage committed cells.

In humans, the thymus is the primary lymphoid organ able to support the development of T cells through its three-dimensional (3D) organization of the thymic stromal cells. Since a remarkable number of similarities are shared between the thymic epithelial cells (TECs) and skin-derived keratinocytes and fibroblasts, in this study we used human keratinocytes seeded with fibroblasts on the 3D poly ε-caprolactone scaffold to evaluate their ability to replace TECs in supporting T-cell differentiation from human haematopoietic stem cells (HSCs). We observed that in the multicellular biocomposite, early thymocytes expressing CD7(+)CD1a(+), peculiar markers of an initial T-cell commitment, were de novo generated.

Biological and clinical relevance of miRNA expression signatures in primary plasma cell leukemia.

Purpose: Primary plasma cell leukemia (pPCL) is a rare and very aggressive form of plasma cell dyscrasia. To date, no information on microRNA (miRNA) expression in pPCL has been reported. This study aimed at investigating the involvement of miRNAs in pPCL and their possible relationship with higher tumor aggressiveness.

Transcriptional characterization of a prospective series of primary plasma cell leukemia revealed signatures associated with tumor progression and poorer outcome.

Purpose: Plasma cell leukemia (PCL) is a rare form of plasma cell dyscrasia that presents either as a progression of previously diagnosed multiple myeloma, namely secondary PCL, or as initial manifestation of disease, namely primary PCL (pPCL). Although the presenting signs and symptoms include those seen in multiple myeloma, pPCL is characterized by several aspects that define a more aggressive course. Here, we have investigated the transcriptome of pPCLs and correlated differential expression profiles with outcome to provide insights into the biology of the disease.

Genome-wide analysis of primary plasma cell leukemia identifies recurrent imbalances associated with changes in transcriptional profiles.

Primary plasma cell leukemia (pPCL) is a rare, yet aggressive form of de novo plasma cell tumor, distinct from secondary PCL (sPCL) which represents a leukemic transformation of pre-existing multiple myeloma (MM). Herein, we performed a comprehensive molecular analysis of a prospective series of pPCLs by means of FISH, single nucleotide polymorphism (SNP) array and gene expression profiling (GEP). IGH@ translocations were identified in 87% of pPCL cases, with prevalence of t(11;14) (40%) and t(14;16) (30.

Role of the common γ chain in cell cycle progression of human malignant cell lines.

The γ-chain (γc) is a transducing element shared between several cytokine receptors whose alteration causes X-linked severe combined immunodeficiency. Recently, a direct involvement of γc in self-sufficient growth in a concentration-dependent manner was described, implying a direct relationship between the amount of the molecule and its role in cell cycle progression. In this study, we evaluate whether γc expression could interfere in cell cycle progression also in malignant hematopoietic cells.

Polymorphisms of the CYP1A1, CYP2E1 and XRCC1 genes and cancer risk in a Southern Italian population: a case-control study.

Background: Polymorphisms in genes encoding enzymes involved in xenobiotic metabolism and/or in cellular defenses against carcinogen-induced DNA damage play an important role in determining individual cancer susceptibility. However, their distribution and association with cancer susceptibility can vary in different populations.

Materials And Methods: A case-control study including 290 cancer patients (cases) and 242 controls was performed to evaluate the relationship between polymorphisms of cytochrome P450 (CYP)1A1 and CYP2E1 and X-ray repair complementing defective repair in Chinese hamster cells (XRCC)1 genes and the risk of developing cancer in a Southern Italian (Basilicata) population.

Positive effects on hematopoiesis in patients with myelodysplastic syndrome receiving deferasirox as oral iron chelation therapy: a brief review.

Iron overload is a frequent consequence in transfusion-dependent myelodysplastic syndromes (MDSs), which often requires iron chelation therapy (ICT). Interestingly, ICT may sometimes induce a hematologic improvement that leads to significant reduction or complete interruption of blood transfusions. This phenomenon has been recently described in MDS treated with the new oral chelator deferasirox.

Modulation of CD20 antigen expression after rituximab treatment: a retrospective study in patients with chronic lymphocytic leukemia.

Background: CD20 antigen down-modulation by anti-CD20 rituximab treatment is a well-recognized phenomenon in patients with non-Hodgkin's lymphoma. However, few data are currently available on this topic in other lymphoproliferative disorders, in particular in chronic lymphocytic leukemia (CLL).

Objective: The aim of this study was to establish how many patients with CLL show a disappearance of CD20 antigen after salvage treatment with rituximab and its possible clinical significance.

Response to recombinant erythropoietin alpha, without the adjunct of granulocyte-colony stimulating factor, is associated with a longer survival in patients with transfusion-dependent myelodysplastic syndromes.

This was a retrospective, comparative study focused on the extended follow-up of 192 transfusion-dependent patients with myelodysplastic syndromes treated (n. 83) or not treated (n. 109) with recombinant erythropoietin alpha (r-EPO) as single agent during the course of their disease.

GSTM1 and NAT2 polymorphisms and colon, lung and bladder cancer risk: a case-control study.

Background: Glutathione S-transferase M1 (GSTM1) and N-acetyltransferase-2 (NAT2) are phase II enzymes involved in the metabolism of xenobiotics and whose polymorphisms have been related to individual cancer risks.

Patients And Methods: A case-control study was performed including 92 colon, 75 lung and 23 bladder cancer patients and 121 corresponding controls to verify the existence of an association between the main genetic polymorphisms of GSTM1 and NAT2 and the risk to develop cancer. Genomic DNA, isolated from 5 mL whole blood, was used to study GSTM1 and NAT2 polymorphisms using multiplex PCR and a PCR-RFLP technique, respectively.

Polymorphisms of the DNA repair genes XRCC1 and XRCC3 and risk of lung and colorectal cancer: a case-control study in a Southern Italian population.

Background: Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with a higher risk of developing cancer. Studies on the association between DNA repair gene polymorphisms and lung and colorectal cancer risk appear to be very limited. This study was designed to examine the polymorphisms associated with two DNA repair genes, namely XRCC1 Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met, and to investigate their role as susceptibility markers for lung and colorectal cancer.