What are the roles of global DNA and APC 2 gene promotor hypermethylation in multiple myeloma?

BACKGROUND: In today's practice, gene-based approaches come to the fore in the determination of prognosis and treatment preferences of multiple myeloma (MM). DNA methylation is one of the new approach parameters. DNA methylation occurs by the addition of a methyl group to cytosines in CpG dinucleotides. In this study, besides comparing the global DNA and APC 2 gene promotor hypermethylation between our patients with MM and healthy control group, we aimed to demonstrate the effect of hypermethylation on MM treatment responses and survival. METHODS AND RESULTS: 38 patients diagnosed with MM between January 2016 and January 2020 and 50 healthy controls were included in the study. The initial hypermethylation of the patients and the healthy control group were statistically analyzed. In addition, the increase in hypermethylation in the MM group before and after the first series of treatments were analyzed within themselves. There is a significant difference between the patients with MM diagnosis and the healthy control group in terms of the initial global hypermethylation (P = 0.001). In patients with MM, hypermethylation was significantly higher. Global hypermethylation in the post-treatment measurements was significantly increased in comparison to the pre-treatment state (P = 0.012). In terms of APC 2 promotor gene-specific hypermethylation, no significant differences were detected between pre- and post-treatment values (P = 0.368). CONCLUSIONS: This study represents valuable data with the initial global DNA hypermethylation results in the MM patient group and the increase in hypermethylation post-treatment. it will shed light on future studies.

A new parameter in multiple myeloma: CYP3A4*1B single nucleotide polymorphism.

Multiple myeloma (MM) is a disease caused by malignant plasma cells, causing free light chain release accompanying the increase in monoclonal immunoglobulin. Cytochrome P450 (CYP) is one of the large and functional enzyme families composed of various hemoproteins. This protein network has been shown to play a role in many treatment steps in current practices. We aimed to investigate the relationship between genotypes of CYP3A4*1B and treatment response and prognosis of MM. Seventy-two patients diagnosed with MM between January 2016 and 2020 and 100 healthy people to create a control group participated in our study. Genotypes were classified in 3 separate groups as NN, MN, and MM. Both PFS and OS were significantly higher in the NN genotype (p = 0.001, p = 0.014). Being under the age of 65 was 27.988 times more protective for OS and 4.496 times for PFS (p = 0.006, p = 0.017). NN genotype was shown to be 41.666-fold protective for OS and 3.144-fold protective for PFS (p = 0.004, p = 0.030). This study demonstrated that CYP3A4*1B NN genotype, which is an important cytochrome p450 member for the treatment of MM, was 41.666-fold protective for OS and 3.144-fold protective for PFS. It was shown in this study for the first time in the literature as a valuable contribution.

Role of MIF-173G/C and Mbl2 Codon 54A/B Variants in the Risk of Multiple Myeloma: An Association Study.

BACKGROUND: Multiple myeloma (MM) is a malignant disease manifested by the clonal proliferation of atypical plasma cells. Macrophage inhibitory factor (MIF) is one of the pleiotropic regulators in various biological and cellular processes. Mannose-binding lectin (MBL) is a crucial protein involved in the lectin pathway of the immune system. OBJECTIVE: We aimed to assess whether variants of MIF and MBL2 genes are associated with MM among a Turkish population. METHODS: We analyzed the MIF-173G/C (rs755622) and MBL2 codon 54A/B (rs1800450) variants in 200 patients with MM and 200 healthy control subjects using a polymerase chain reaction (PCR) followed by restriction endonuclease digestion. There was also an evaluation of the patients undergoing autologous stem-cell transplantation (ASCT) for these variants. RESULTS: AA and BB genotypes of MBL2 codon 54A/B increased in the patients as compared to the controls (p=0.008, p=0.001, respectively). The subjects carrying AA and BB genotypes of MBL2 were at high risk of development of susceptibility to MM by 7.377 and 8.812 times, respectively. The distribution of MBL2 codon 54A/B alleles was similar between the groups (p>0 .05). There was no statistical difference between the patients and controls in the genotype and allele frequencies of the MIF- 173G/C variant (p>0 .05). The patients undergoing ASCT, MBL2 codon 54A/B AA and BB genotypes also showed association with increased risk for MM (p=0.004, p=0.001, respectively). CONCLUSION: As far as we know, this is the first report of the study on an association between these variants and MM in our population. Our results indicate that the MBL2 codon 54A/B variant may be associated with susceptibility to MM.

Evaluation of Cardiac Parameters in Bone Marrow Transplant Patients: Effect of Pulmonary Artery Pressure on Survival

Objective: Hematopoietic stem cell transplantation (HSCT) is a choice of treatment for malignant and non-malignant diseases. After HSCT, some complications may develop in patients. Cardiac complications are particularly important. The aim of this study was to investigate whether systolic pulmonary artery pressure (PAP) is a marker for overall survival (OS) in HSCT patients. Materials and Methods: In our study, 428 HSCT patients were evaluated. Ejection fraction (EF) and PAP values were investigated during symptom-oriented echocardiography in the pre-HSCT and post-HSCT periods. Results: Pre-HSCT EF values were similar between the groups. In patients with autologous HSCT (auto-HSCT) (PAP >25 mmHg), it was found that the 5-year mortality rate was 48.6%, while in the other group (PAP <25 mmHg) the 5-year mortality was 25.5%. There was a significant association between 5-year mortality rate and PAP level (p<0.046) in the auto-HSCT group. OS was 38% in the pre-auto-HSCT period with PAP values of >25 mmHg, while OS was 61% in the pre-auto-HSCT period with PAP values of <25 mmHg (p<0.001). We determined that there was a statistically significant difference between OS and PAP levels in patients with auto-HSCT. Five-year mortality rate and OS were not significantly different in patients undergoing allogeneic HSCT (allo-HSCT) (p>0.05). Conclusion: Our results suggest that pre-HSCT PAP value is an important risk factor for mortality and OS in patients undergoing auto-HSCT.