Multiple myeloma results from the degeneration of a single plasma cell whose clones spread throughout the bone marrow. Overall, the disease occurs very rarely. However, it is one of the most common tumors of bone and bone marrow. Intensive research is being conducted into the non-Hodgkin’s lymphoma group in order to improve the prognosis of those affected in the long term.
Previous work has shown that impaired maturation of neutrophils is associated with progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). Hematopoietic stem and progenitor cells (HSPCs) participate in multiple ways in the primary immune response to various pathological conditions and serve as a link to the accumulation of myeloid-derived suppressor cells (MDSCs). Recently, the first neutrophil progenitor cells were found in peripheral blood, characterized by the expression of CD71 as a marker of the early stages of neutrophil proliferation. These findings could potentially play an important biological and clinical role in identifying MM patients with worse outcomes. Therefore, it was investigated whether measurement of myeloid precursors in the peripheral blood of patients with plasma cell dyscrasias by flow cytometry could be a marker to identify patients with myeloid dysplasia features independent of the therapy administered [1].
Fifty patients with plasma cell dyscrasias were recruited for this purpose and followed up for a median of 13.8 months. Samples from 23 healthy donors were analyzed as a control group. A progressive increase in circulating CD15+CD71+CD117+ cells was observed in MM patients compared to MGUS and healthy donors. Patients with a high proportion of CD15+CD71+CD117+ cells were found to have higher ISS and lower hemoglobin levels at diagnosis compared with patients with a low proportion of CD15+CD71+CD117+ cells and were more likely to have high-risk FISH. However, univariate survival analysis failed to identify a high proportion of CD15+CD71+CD117+ cells as a predictor of progression or overall survival. That is, CD15+CD71+CD117+ myeloid progenitor cells are increased in MGUS and MM patients compared with healthy individuals, with no apparent impact on clinical outcomes.
The role of leptin in MM
Leptin is mainly produced by adipose tissue and released into the bloodstream. Circulating leptin binds to the leptin receptor (LEPR) in the brain, which activates signaling pathways that inhibit food intake and promote calorie consumption. The gene for the leptin receptor (LEPR, also known as Ob-R) is located on 1p31. DNA methylation consists of the addition of a methyl group at position 5 of the pyrimidine ring of cytosines before a guanine (dinucleotide CpG), which is catalyzed by DNA methyltransferases. Methylation of cytosine at CpG sites is an important epigenetic modification that can repress gene expression. A study now investigated the role of gene polymorphisms of leptin and LEPR in MM patients [2].
A total of 300 MM patients and 170 subjects who formed a healthy control group were included in this study. In the statistical analysis to investigate the effects of leptin and LEPR gene polymorphisms on disease susceptibility, it was found that GA and AA genotypes of leptin gene were significantly higher in the patient group compared with the healthy control subjects. Regarding the methylation of -31 NT and -51 NT of the leptin gene, it was observed that the methylation of -51 NT was significantly higher in the healthy controls. Survival analysis brought to light that progression-free survival of patients with the GG genotype of the LEPR gene was significantly shorter compared to other patients, while there was no effect on overall survival. Accordingly, the results showed that MM and leptin polymorphisms have significant features affecting both disease susceptibility and treatment response.
Prognostic factors under the microscope
MM is a very heterogeneous disease, with almost all patients eventually relapsing and/or becoming refractory to treatment. Several studies have identified factors that determine the prognosis of patients with RRMM. However, an up-to-date synthesis of the available evidence was lacking. This has now been made up for [3]. The most commonly studied factors in the 125 included studies were disease stage, age, previous lines of therapy, best response to index therapy, cytogenetic risk, lactate dehydrogenase, extramedullary disease/plasmacytoma (EMP), and performance status (PS).
Poorer survival was associated with higher disease stage, older age, more prior lines of therapy, poorer response, high-risk cytogenetics, elevated LDH levels, presence of EMP, and poorer PS. In contrast, poorer response was associated with higher disease stage, younger age, more prior lines of therapy, high-risk cytogenetics, and poorer PS.
Congress: 28th Annual Congress of the European Hematology Association (EHA) 2023
Literature:
- Parinello NL, Duminuco A, Marino S, et al: Circulating CD71+ myeloid percursors in mgus and multiple myeloma: a prospecitive survey. HemaSphere 2023; 7(S3): 3984-3985.
- Serin I, Oyaci Y, Pehlivan M, et al: Hof effective are leptin gene polymorphisms and methylation during the course of multiple myeloma (MM)? HemaSphere 2023; 7(S3): 3987-3988.
- Kumar S, Leleu X, Weisel K, et al: Systematic literature review of prognostic factors for relapsed/refractory multiple myeloma. HemaSphere 2023; 7(S3): 4017-4018.
InFo ONCOLOGY & HEMATOLOGY 2023; 11(4): 22 (published 12/9/2013, ahead of print).
