High prevalence of heparin induced thrombocytopenia with thrombosis among patients with essential thrombocytemia carrying V617F mutation.

Arterial and venous complications are major causes of morbidity and mortality in myeloproliferative neoplasms (MPNs). MPNs patients, frequently receive heparin. Heparin-induced thrombocytopenia (HIT) is a rare but potentially life-threatening complication resulting in a severe acquired thrombophilic condition. We carried out a retrospective analysis to evaluate occurrence of new thrombotic events during heparin therapy in essential thrombocythemia (ET) patients. We studied 108 ET patients on heparin for treatment of previous thrombotic events or in thromboprophilaxis. Fifty-eight of them carried JAK 2 V617F mutation while 50 patients were without V617F mutation. Ten patients, among those with JAK 2 V617F mutation after a median of 10 days from heparin treatment presented a platelet drop, new thrombotic events and in 10/10 cases heparin-related antibodies were found. In the other group, two patients (4%) presented a platelet drop, thrombotic manifestations and heparin related antibodies. Our data show that HIT is more frequent, during heparin treatment, in patients with ET carrying V617F mutation, as compared with patients without mutations (P = 0.029). ET with V617F mutation seems to be associated with higher risk of thrombotic complications during heparin treatment. Monitoring platelet counts very closely during the course of heparin is essential especially in ET patients in which platelet drop may be hidden by constitutional thrombocytosis

An integrative genomic approach reveals coordinated expression of intronic miR-335, miR-342, and miR-561 with deregulated host genes in multiple myeloma

<p>Abstract</p> <p>Background</p> <p>The role of microRNAs (miRNAs) in multiple myeloma (MM) has yet to be fully elucidated. To identify miRNAs that are potentially deregulated in MM, we investigated those mapping within transcription units, based on evidence that intronic miRNAs are frequently coexpressed with their host genes. To this end, we monitored host transcript expression values in a panel of 20 human MM cell lines (HMCLs) and focused on transcripts whose expression varied significantly across the dataset.</p> <p>Methods</p> <p>miRNA expression was quantified by Quantitative Real-Time PCR. Gene expression and genome profiling data were generated on Affymetrix oligonucleotide microarrays. Significant Analysis of Microarrays algorithm was used to investigate differentially expressed transcripts. Conventional statistics were used to test correlations for significance. Public libraries were queried to predict putative miRNA targets.</p> <p>Results</p> <p>We identified transcripts specific to six miRNA host genes (<it>CCPG1</it>, <it>GULP1</it>, <it>EVL</it>, <it>TACSTD1</it>, <it>MEST</it>, and <it>TNIK</it>) whose average changes in expression varied at least 2-fold from the mean of the examined dataset. We evaluated the expression levels of the corresponding intronic miRNAs and identified a significant correlation between the expression levels of <it>MEST</it>, <it>EVL</it>, and <it>GULP1 </it>and those of the corresponding miRNAs miR-335, miR-342-3p, and miR-561, respectively. Genome-wide profiling of the 20 HMCLs indicated that the increased expression of the three host genes and their corresponding intronic miRNAs was not correlated with local copy number variations. Notably, miRNAs and their host genes were overexpressed in a fraction of primary tumors with respect to normal plasma cells; however, this finding was not correlated with known molecular myeloma groups. The predicted putative miRNA targets and the transcriptional profiles associated with the primary tumors suggest that <it>MEST</it>/miR-335 and <it>EVL/</it>miR-342-3p may play a role in plasma cell homing and/or interactions with the bone marrow microenvironment.</p> <p>Conclusion</p> <p>Our data support the idea that intronic miRNAs and their host genes are regulated dependently, and may contribute to the understanding of their biological roles in cancer. To our knowledge, this is the first evidence of deregulated miRNA expression in MM, providing insights that may lead to the identification of new biomarkers and altered molecular pathways of the disease.</p

Functional differences between dendritic cells derived from CD34 + bone marrow and peripheral blood stem cells

Background and Objectives. It has been previously demonstrated that dendritic cells (DCs) are characterized by an immature stage with high antigen internalization capacity, followed by a mature stage with predominantly immunostimulatory ability. The shift from the immature to the mature state can be induced in vitro by the addition of tumor necrosis factor-␣ (TNF␣). The aim of our study was to investigate the maturation steps of DCs obtained from CD34 + cells from peripheral blood stem cells (PBSC) and bone marrow (BM)

Biosimilar epoetin alfa increases haemoglobin levels and brings cognitive and socio-relational benefits to elderly transfusion-dependent multiple myeloma patients: results from a pilot study

Anaemia is a complication reported in up to 70% of the multiple myeloma patients (MM), with remarkable clinical, cognitive and socio-relational consequences. Anaemia relates to the course of MM, normalizing in patients during remission and reappearing in relapsing/non-responding patients. In a pilot study with 31 patients with MM and transfusion-dependent anaemia, we evaluated the effects of Binocrit (biosimilar epoetin alfa) on transfusions, haemoglobin levels, mental status (mini-mental state evaluation) and the patients\u2019 social-relational functioning and quality of life (QoL). Within a 12-week interval, patients received 40.000\ua0U Binocrit once a week. Binocrit significantly decreased the incidence of transfusion, regardless of the patients\u2019 transfusion history, and significantly increased haemoglobin levels (before-and-after-treatment median haemoglobin values = 8.20 vs. 9.40\ua0g/dl, respectively; Wilcoxon Z test, p\ua0<\ua0.001). A comparatively greater increment in haemoglobin levels among patients who responded to first vs. additional lines of chemotherapy was also observed. Importantly, we additionally found moderate-to-strong positive associations between increments in haemoglobin levels and corresponding increments both in psychological well-being and QoL (FACT-An scores) and the patients\u2019 cognitive status (mini-mental state evaluation scores). After statistically controlling for possible concurrent benefits of anti-myeloma therapy, increments in haemoglobin levels clearly predicted both increments in socio-relational FACT-An scores (Spearman\u2019s rho\ua0=\ua00.60, p\ua0<\ua0.001) and in cognitive functioning scores (Spearman\u2019s rho\ua0=\ua00.49, p\ua0<\ua0.006). Binocrit thus appears as an effective, well-tolerated agent for the management of myeloma anaemia, whose documented benefits include amelioration of anaemia, reduction in transfusion, and improvements in the patients\u2019 social-relational functioning and cognitive well-being