Progesterone may be a regulator and B12 could be an indicator of the proximal D4Z4 repeat methylation status on 4q35ter.

Facioscapulohumeral dystrophy (FSHD) has a hypomethylation-related epigenetic background and exhibits a different course in male and female patients. The differences between males and females have been linked to the levels of sex hormones. This study is the first to investigate the possible effect of these hormones on methylation status. We hypothesized that the levels of sex-related hormones, estradiol, testosterone, progesterone, and prolactin might be associated with the methylation status of the proximal part of the D4Z4. We also investigated the effect of fT3, folic acid, and vitamin B12 levels. We collected blood from 28 FSHD patients and 28 controls. DNA was extracted from each individual for bisulfite methylation analysis and serum was separated for biochemical analysis of estradiol, testosterone, progesterone, prolactin, fT3, folic acid, and B12 analysis. Methylation analysis was specified to the DR1, 5P regions and the proximal region covering both DR1 and 5P. Methylation levels were compared between FSHD patients and controls. The correlation of methylation levels with estradiol, testosterone, progesterone, prolactin, fT3, folic acid, and B12 was investigated. We found that the 5P region and the proximal region were significantly hypomethylated in FSHD patients compared to the controls, but not the DR1 region. Male patients exhibited a significant reduction in DNA methylation compared to male controls. Older FSHD patients exhibited a notable decrease in fT3 levels and hypomethylation of the 5P region. Analyses of each CpG revealed seven hypomethylated positions that were significantly different from the control group. Two of the positions demonstrated a correlation with progesterone in the control group. With the exception of one position, the methylation levels were inversely correlated with vitamin B12 in FSHD patients. The results of our study indicate that the methylation of the proximal D4Z4 region, particularly at specific positions, may be associated with progesterone. In addition, vitamin B12 may be an indicator of hypomethylation. We suggest that examining position-specific methylations may be a useful approach for the development of epigenetic treatment modalities.

Analysis of DUX4 Expression in Bone Marrow and Re-Discussion of DUX4 Function in the Health and Disease.

OBJECTIVE: DUX4 is an embryonic transcription factor (TF) later silenced in somatic tissues, while active in germline testis cells. Re-expression in somatic cells has been revealed to be present in pathologic conditions such as dystrophy, leukemia, and other cancer types. Embryonic cells, cancer cells and testis cells that show DUX4 expression are pluri-multipotent cells. This lead us to question "Could DUX4 be a TF that is active in certain types of potent somatic cells?" As a perfect reflection of the potent cell pool, we aimed to reveal DUX4 expression in the bone marrow. MATERIAL AND METHOD: Bone marrow aspiration materials of seven healthy donors aged between 3 and 32 (2 males/5 females) were investigated with qPCR analysis after RNA isolation for the presence of DUX4 full length mRNA expression. Samples have been investigated for protein existence of DUX4 via immunohistochemistry in two donors that had sufficient aspiration material. RESULTS: DUX4 mRNA expression was present in all donors, with higher expression compared to B-actin. DUX4 positive stained cells were also detected by immunohistochemistry. CONCLUSION: With these results, novel expression for DUX4 in hematopoietic tissue is described. Further studies on the function of DUX4 in hematopoietic cells can shed light on DUX4-related pathways, and contribute to the treatment of DUX4-related diseases such as B-ALL, other cancers, and facioscapulohumeral muscular dystrophy.

Promising Perspective to Facioscapulohumeral Muscular Dystrophy Treatment: Nutraceuticals and Phytochemicals.

Facioscapulohumeral Muscular Dystrophy (FSHD) is in the top three list of all dystrophies with an approximate 1:8000 incidence. It is not a life-threatening disease; however, the progression of the disease extends over being wheelchair bound. Despite some drug trials continuing, including DUX4 inhibition, TGF-ß inhibition and resokine which promote healthier muscle, there is not an applicable treatment option for FSHD today. Still, there is a need for new agents to heal, stop or at least slow down muscle wasting. Current FSHD studies involving nutraceuticals as vitamin C, vitamin E, coenzyme Q10, zinc, selenium, and phytochemicals as curcumin or genistein, daidzein flavonoids provide promising treatment strategies. In this review, we present the clinical and molecular nature of FSHD and focus on nutraceuticals and phytochemicals that may alleviate FSHD. In the light of the association of impaired pathophysiological FSHD pathways with nutraceuticals and phytochemicals according to the literature, we present both studied and novel approaches that can contribute to FSHD treatment.

Conventional Cytogenetics and Interphase Fluorescence In Situ Hybridization Results in Multiple Myeloma: A Turkey Laboratory Analysis of 381 Cases.

Multiple myeloma (MM) is an uncontrolled proliferation of plasma cells and these cells play an important role in the immune system. In this research, we retrospectively analyzed cytogenetic abnormalities in 381 patients with MM. Conventional cytogenetic analysis was successful in 354 patients (92.9%). Chromosomal abnormalities were detected in 31.9% (113/354) and 45.8% (116/253) of patients screened with conventional cytogenetics and FISH, respectively. Of 113 patients with chromosomal abnormalities, 31 patients (27.4%) had hyperdiploid and 26 of 31 patients with hyperdiploidy had both numerical and structural anomalies. On the other hand, non-hyperdiploidy was observed in 62 patients (54.8%). The most common gains of chromosomes were 15, 9, 19 followed by 3, 5, 11, and 21. Whole chromosome losses were also frequent involving Y, 13 and 22 chromosomes. In our patients, 1q gain was determined in a total of 25 patients (22%), including 7 structural abnormalities and 19 unbalanced translocations causing complete or partial duplication of the long arm of chromosome 1. Although the breakpoints were different, t(1;5) balanced translocation and unbalanced translocations of t(1;2), t(1;3), t(1;7), t(1;16) and t(1;19) were observed twice. The most common structural abnormality was the deletion of the short arm of chromosome 13 (13q) or monosomy of chromosome 13 (-13) (24.1%, 61/253) in patients evaluated by FISH. Deletion involving chromosome 17p (del 17p) or monosomy of chromosome 17 (-17) were found in 31 (12.3%) patients. Translocations involving IgH regions were as follows: t(11;14)(q13;q32.33) in 22 (8.7%), t(4;14)(p16.3;q32.33) in 22 (8.7%) and t(14;16)(q32.33;q23.1) in 2 (0.8%) patients. In addition, t(14;17)(q32;q21) translocation was detected in a multiple myeloma patient for the first time in this study. There are a limited number of large study groups including both cytogenetic and FISH findings in MM patients. As the number of these studies increases, it is thought that new cytogenetic data can be guiding especially in clinical risk determination.