Growth Differentiation Factor 15 in Multiple Myeloma: A Microenvironment Factor Predictive of Response to Treatment?

2013 ◽  
Vol 131 (3) ◽  
pp. 170-172
Author(s):  
Jill Corre
Keyword(s):  
Multiple Myeloma ◽  
Response To Treatment ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

scholarly journals Association between Circulating Growth Differentiation Factor 15 and Cirrhotic Primary Biliary Cholangitis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Zhanyi Li ◽  
Yu Liu ◽  
Xiangyong Li ◽  
Yuankai Wu ◽  
Fangji Yang ◽  
...  
Keyword(s):  
Serum Levels ◽  
Response To Treatment ◽  
Primary Biliary Cholangitis ◽  
Strongly Correlated ◽  
Weight Changes ◽  
Adequate Treatment ◽  
Growth Differentiation Factor 15 ◽  
Reactive Protein ◽  
Differentiation Factor ◽  
End Stage

Primary biliary cholangitis (PBC) is a common condition that usually shows a progressive course towards cirrhosis without adequate treatment. Growth differentiation factor 15 (GDF15) plays multiple roles in various pathological conditions. The overall role of circulating GDF15 in cirrhotic PBC requires further investigation. Twenty patients with cirrhotic PBC, 26 with non-cirrhotic PBC, and 10 healthy subjects were enrolled between 2014 and 2018, and the serum levels of GDF15 were measured via enzyme immunoassay. The correlations between serum GDF15, weight, biochemical parameters, and the prognosis were analysed. Serum levels of GDF15 were significantly higher in cirrhotic PBC patients than in non-cirrhotic PBC patients or healthy controls ( p = 0.009 and p < 0.001 , respectively). The circulating GDF15 levels strongly correlated with weight changes ( r = − 0.541 , p = 0.0138 ), albumin ( r = − 0.775 , p < 0.0001 ), direct bilirubin ( r = − 0.786 , p < 0.0001 ), total bile acids ( r = 0.585 , p = 0.007 ), and C-reactive protein ( r = 0.718 , p = 0.0005 ). Moreover, circulating GDF15 levels strongly correlated with the Mayo risk score ( r = 0.685 , p = 0.0009 ) and Model for End-stage Liver Disease score ( r = 0.687 , p = 0.0008 ). Determined by the area under the receiver operating characteristic curves, the overall diagnostic accuracies of GDF15 were as follows: cirrhosis = 0.725 (>3646.55 pg/mL, sensitivity: 70.0%, specificity: 69.2%), decompensated   cirrhosis = 0.956 (>4073.30 pg/mL, sensitivity: 84.62%, specificity: 100%), and cirrhotic biochemical non-responders = 0.835 (>3479.20 pg/mL, sensitivity: 71.43%, specificity: 92.31%). GDF15 may be a useful and integrated biochemical marker to evaluate not only the disease severity and prognosis but also the nutrition and response to treatment of cirrhotic PBC patients, and its overall performance is satisfactory. Therapy targeting GDF15 is likely to benefit cirrhotic PBC patients and is worth further research.

The TGF- β Family Member Growth Differentiation Factor 15 (GDF15) Regulates the Self-Renewal of Multiple Myeloma Cancer Stem Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2954-2954
Author(s):  
Toshihiko Tanno ◽  
Akil Merchant ◽  
Jasmin R. Agarwal ◽  
Qiuju Wang ◽  
William Matsui
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cancer Stem Cells ◽  
The Self ◽  
Disease Stage ◽  
Dependent Manner ◽  
Self Renewal ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

Abstract Abstract 2954 Multiple myeloma (MM) cancer stem cells (CSCs) possess both enhanced tumorigenic potential and relative drug resistance suggesting they play a major role in disease relapse and progression. Therefore, a better understanding of the processes regulating MM CSCs may lead to the development of novel therapies that prevent tumor regrowth and improve long-term outcomes. Normal stem cells are tightly regulated by factors within the local microenvironment that include both soluble factors and direct contact with accessory cells. However, external factors regulating MM CSCs have not been identified. Recent studies have demonstrated that stromal cells in the MM bone marrow microenvironment secrete growth differentiation factor 15 (GDF15), a member of the TGF-b family. We initially studied the role of this cytokine in the pathogenesis of MM by examining circulating GDF15 levels in MM patients. Compared to healthy volunteers, we found that median GDF15 levels were significantly increased in MM patients (821 vs. 390 pg/ml; n=16; p<0.05) and increased with disease stage (Stage II=585 pg/ml, Stage III=1, 004 pg/ml). To examine the functional effects of GDF15 on MM cells, we cultured human MM cell lines (NCI-H929, RPMI 8226) with recombinant GDF15 and found that it induced the expansion of isolated CD138neg MM CSCs in a dose-dependent manner but had little impact on the growth of CD138+ plasma cells (Fig). Furthermore, GDF15 enhanced clonogenic myeloma growth as evidenced by increased colony formation that was maintained during serial replating, a surrogate for self-renewal. This effect appeared to be GDF15 specific since it could be blocked using anti-GDF15 antibody. Similarly, GDF15 treatment increased the in vitro clonogenic growth of MM CSCs from primary clinical bone marrow specimens. We also investigated the down-stream cellular pathways potentially mediating the effects of GDF15 and found that it activates the AKT signaling pathway known to improve the self-renewal of embryonic (ES) and normal hematopoietic stem cells. GDF15 also induced expression of the SOX2 transcription factor known to be upregulated in CD138neg MM CSCs. Since SOX2 is required for the self-renewal of ES cells and the generation of induced pluripotent stem (iPS) cells, its induction by GDF15 may also increase the self-renewal of MM CSCs. GDF15 is the first soluble factor identified that regulates MM CSCs, and its effects are mediated by the activation of highly conserved self-renewal programs. Disclosures: No relevant conflicts of interest to declare.

Serum Growth Differentiation Factor 15 Levels in Newly Diagnosed Multiple Myeloma Patients

2013 ◽  
Vol 131 (3) ◽  
pp. 173-178 ◽  
Author(s):  
Pinar Tarkun ◽  
Elif Birtas Atesoglu ◽  
Ozgur Mehtap ◽  
Mahmut Mert Musul ◽  
Abdullah Hacihanefioglu
Keyword(s):  
Multiple Myeloma ◽  
Newly Diagnosed ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

scholarly journals Study of Growth Differentiation Factor 15(GDF15) and Some Biochemical Parameters in Multiple Myeloma Patients Subjected to Chemotherapy with Added Paroxetine in-Vitro

2020 ◽  
Vol 23 (2) ◽  
pp. 18-25
Author(s):  
Zahraa A. H. Al-Timeeme ◽  
◽  
Wisam Kadhum H. Alhashemi ◽  
Alaadin Sahham Naji ◽  
Ahmed Fadhil Neama ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Biochemical Parameters ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor

Growth-differentiation factor-15 nach TIA oder ischämischem Schlaganfall bestimmt das klinische Outcome

2009 ◽  
Vol 36 (S 02) ◽  
Author(s):  
H Worthmann ◽  
T Kempf ◽  
AB Tryc ◽  
A Goldbecker ◽  
YT Ma ◽  
...  
Keyword(s):  
Growth Differentiation Factor 15 ◽  
Differentiation Factor
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