Evaluating the Relationship of GDF-15 with Clinical Characteristics, Cardinal Features, and Survival in Multiple Myeloma

Abstract

Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-β superfamily, participates in processes associated with myeloma development and its end-organ complications. It plays a significant role in both physiological and abnormal erythropoiesis and regulates iron homeostasis through modulation of hepcidin. It is abnormally secreted in marrow stromal cells of patients with multiple myeloma (MM), which may reflect the tumor microenvironment. We analyzed the associations of serum GDF-15 with clinical characteristics of 73 MM patients (including asymptomatic MM) and the laboratory indices of renal function, anemia, and inflammation. Baseline serum GDF-15 was studied as the predictor of two-year survival. We defined five clinically relevant subgroups of patients (symptomatic MM only, patients with and without remission, patients on chemotherapy, and without treatment). Increased GDF-15 concentrations were associated with more advanced MM stage, anemia, renal impairment (lower glomerular filtration and higher markers of tubular injury), and inflammation. Most of the results were confirmed in the subgroup analysis. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin were associated with GDF-15 independently of other variables. In the studied MM patients, GDF-15 did not significantly predict survival ( p = 0.06 ). Our results suggest that serum GDF-15 reflects myeloma burden and shares a relationship with several markers of prognostic significance, as well as major manifestations.

GDF15: an emerging modulator of immunity and a strategy in COVID-19 in association with iron metabolism

“…MM is a malignant condition that manifests with bone disease, renal failure, and anemia. It has been demonstrated that the serum concentration of GDF15 in patients with MM is positively correlated with the established prognostic factors of the disease, and that these concentrations were significantly higher in the studied patients with anemia and inversely correlated with blood hemoglobin and serum iron [64]. A recent report showed that the levels of GDF15 mRNA were increased during erastin-induced ferroptosis.…”

Anemia with elevation of growth differentiation factor-15 level in linezolid treated multidrug-resistant tuberculosis: Case series of three patients

“…These changes were observed at 2nd week of treatment, preceding the development of anemia (at the 4th to 12th week). Correlation of high level of GDF-15 with low hemoglobin level had been reported in patients with anemia of chronic disease, ineffective erythropoiesis, multiple myeloma, heart failure and chronic kidney disease [Theurl, 2010 #63][Tanno, 2010 #64][Banaszkiewicz, 2020 #65][Przybyłowski, 2014 #66][Ueland, 2021 #67][Nalado, 2020 #68] [18] , [19] , [20] , [21] , [22] , [23] .…”

TGF-β: an active participant in the immune and metabolic microenvironment of multiple myeloma

“…Also, VCAM-1 and α4β1 integrin not only enhance adherence of MM to BMSCs but also induce IL-6 and RANKL expression by BMSCs, stimulating OCs formation [4,23]. Then, serum-increased levels of GDF-15 are associated with more advanced MM stages [77]. The interaction of OBs and myeloma cells can produce TGF-β to suppress the self-differentiation of OBs [53].…”