POTENTIAL GENETIC AGENT BFL1 FOR TARGETED THERAPY IN CHRONIC LYMPHOCYTIC LEUKEMIA

Background: Many prognostic factors have been identified in chronic lymphocytic leukemia (CLL) but new ones are still desired. The biological characterization of CLL is now being translated into novel treatment strategies. One new prognostic factor, and therapeutic target, may be BFL1. It is both a serum and a molecular marker that contributes to the progression of CLL and its resistance to chemotherapy. The aim of this study was to evaluate the prognostic value of BFL1 and to assess its correlation with other known prognostic markers in CLL for the cladribine and cyclophosphamide regimen (CC). Methods: qPCR TaqMan® Low Density Array was used for gene expression measurements. Assessment of CD38, ZAP70 and BFL-1 proteins expression was done by means of flow cytometry. Serum TK activity was measured by immunoassay. Results: Protein BFL1 expression was found to be significantly higher in CLL patients than healthy volunteers (p=0.001). Moreover its level was significantly higher in patients with no response (NR) to CC therapy (p=0.009). The expression of BFL1 was considerably down regulated during CC treatment and BFL1 mRNA levels were inversely correlated with apoptotic response. In addition, protein BFL1 expression was found to be similar to thymidine kinase (TK) concentration regarding treatment response. As far as other markers are concerned, a positive correlation was identified between BFL1 and TK (r=0.52, p=0.01). Conclusions: Our findings suggest that BFL1 contributes to chemoresistance and may be a co-existing prognostic factor in CLL in the future

Summaries of plenary, symposia, and oral sessions at the XXII World Congress of Psychiatric Genetics, Copenhagen, Denmark, 12-16 October 2014

The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Copenhagen, Denmark, on 12-16 October 2014. A total of 883 participants gathered to discuss the latest findings in the field. The following report was written by student and postdoctoral attendees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported

Research on synthesis of amino acids using new glycine equivalents

-

CRL4^CRBN E3 Ligase Complex as a Therapeutic Target in Multiple Myeloma

Multiple myeloma (MM) is the second most common hematological malignancy with a recurrent clinical course. The introduction of immunomodulatory drugs (IMiDs) was one of the milestones in MM therapy leading to a significant improvement in patients’ prognosis. Currently, IMiDs are the backbone of MM therapy in newly diagnosed and relapsed/refractory settings. It is now known that IMiDs exert their anti-myeloma activity mainly by binding cereblon (CRBN), the substrate receptor protein of the CRL4 E3 ubiquitin ligase (CRL4CRBN) complex. By binding CRBN, IMiDs alter its substrate specificity, leading to ubiquitination and proteasomal degradation of proteins essential for MM cell survival. Following the success of IMiDs, it is not surprising that the possibility of using the CRL4CRBN complex’s activity to treat MM is being further explored. In this review, we summarize the current state of knowledge about novel players in the MM therapeutic landscape, namely the CRBN E3 ligase modulators (CELMoDs), the next generation of IMiDs with broader biological activity. In addition, we discuss a new strategy of tailored proteolysis called proteolysis targeting chimeras (PROTACs) using the CRL4CRBN to degrade typically undruggable proteins, which may have relevance for the treatment of MM and other malignancies in the future

Health behaviors of patients after breast cancer surgery in the Podkarpackie voivodeship

Aim. An evaluation of lifestyle changes (physical activity, diet) in patients after breast cancer surgery. Materials and method. 200 women after breast cancer surgery were surveyed. The respondents were asked whether the surgery caused a change in their diet and physical activity. An analysis was performed concerning the education, place of residence and age of the respondents. Results. Prior to being diagnosed with breast cancer, about one third of the respondents were concerned about their diet and physical activity. After the surgery more than a half of the respondents were concerned about a healthy lifestyle. Women below 50 years old with higher education, who live in a city, were concerned about their diet and physical activity both before and after surgery. Conclusions. As a result of the breast cancer surgery, lifestyle changes were most often found in women aged 50-69 years old with higher education who lived in a city. Statistical relevance of the results was noted