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Published in: Indian Journal of Hematology and Blood Transfusion 1/2021

01-01-2021 | Acute Myeloid Leukemia | Original Article

Prognostic Impact of Serum Growth Differentiation Factor 15 Level in Acute Myeloid Leukemia Patients

Authors: Hany Mohamed Hegab, Amro Mohamed Sedky El-Ghammaz, Mostafa Kamal El-Razzaz, Reham Ali Ali Helal

Published in: Indian Journal of Hematology and Blood Transfusion | Issue 1/2021

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Abstract

Growth differentiation factor 15 (GDF15) plays an important role in cancer pathophysiology and prognosis. However, limited studies analyzed its level and prognostic value in acute myeloid leukemia (AML) patients. This study included 56 adult AML patients. Serum GDF15 level was measured at diagnosis in all patients by enzyme-linked immunosorbent assay. Remission and survival statuses were assessed at 90 days following treatment. GDF15 level was significantly higher in patients than in controls (P < 0.001). GDF15 level correlated positively with age (P < 0.001), hemoglobin level (P = 0.027), and platelet count (P = 0.024). High GDF15 above the median level was associated with inferior OS (P = 0.044) together with high platelet count (P = 0.006) and high bone marrow blast percent (P = 0.038). There was no statistically significant difference between patients with GDF15 above and below the median level regarding DFS (P = 0.881). On multivariate analysis for OS, GDF15 level was an independent risk factor (P = 0.047). In conclusion, serum GDF15 level is significantly elevated in AML patients and high GDF15 level is associated with inferior OS.
Literature
1.
go back to reference Bootcov MR, Bauskin AR, Valenzuela SM et al (1997) MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-superfamily. Proc Natl Acad Sci USA 94:11514–11519PubMed Bootcov MR, Bauskin AR, Valenzuela SM et al (1997) MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-superfamily. Proc Natl Acad Sci USA 94:11514–11519PubMed
2.
go back to reference Berezin AE (2016) Diabetes mellitus related biomarker: the predictive role of growth-differentiation factor-15. Diabetes Metab Syndr 10(1 Suppl. 1):S154–S157PubMed Berezin AE (2016) Diabetes mellitus related biomarker: the predictive role of growth-differentiation factor-15. Diabetes Metab Syndr 10(1 Suppl. 1):S154–S157PubMed
3.
go back to reference Breit SN, Johnen H, Cook AD et al (2011) The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism. Growth Factors 29:187–195PubMed Breit SN, Johnen H, Cook AD et al (2011) The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism. Growth Factors 29:187–195PubMed
4.
go back to reference Mimeault M, Batra SK (2010) Divergent molecular mechanisms underlying the pleiotropic functions of macrophage inhibitory cytokine-1 in cancer. J Cell Physiol 224:626–635PubMedPubMedCentral Mimeault M, Batra SK (2010) Divergent molecular mechanisms underlying the pleiotropic functions of macrophage inhibitory cytokine-1 in cancer. J Cell Physiol 224:626–635PubMedPubMedCentral
5.
go back to reference Buendgens L, Yagmur E, Bruensing J et al (2017) Growth differentiation factor-15 is a predictor of mortality in critically ill patients with sepsis. Dis Markers 2017:5271203PubMedPubMedCentral Buendgens L, Yagmur E, Bruensing J et al (2017) Growth differentiation factor-15 is a predictor of mortality in critically ill patients with sepsis. Dis Markers 2017:5271203PubMedPubMedCentral
6.
7.
go back to reference Döhner K, Döhner H (2008) Molecular characterization of acute myeloid leukemia. Haematologica 93(7):976–982PubMed Döhner K, Döhner H (2008) Molecular characterization of acute myeloid leukemia. Haematologica 93(7):976–982PubMed
8.
go back to reference Schlenk RF, Döhner H (2013) Genomic applications in the clinic: use in treatment paradigm of acute myeloid leukemia. Hematol Am Soc Hematol Educ Program 2013:324–330 Schlenk RF, Döhner H (2013) Genomic applications in the clinic: use in treatment paradigm of acute myeloid leukemia. Hematol Am Soc Hematol Educ Program 2013:324–330
9.
go back to reference Uchiyama T, Kawabata H, Miura Y et al (2015) The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis. Cancer Med 4(10):1558–1572PubMedPubMedCentral Uchiyama T, Kawabata H, Miura Y et al (2015) The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis. Cancer Med 4(10):1558–1572PubMedPubMedCentral
10.
go back to reference Bennett JM, Catovsky D, Daniel MT et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 1976;33(4):451–458 Bennett JM, Catovsky D, Daniel MT et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 1976;33(4):451–458
11.
go back to reference Slovak ML, Kopecky KJ, Cassileth PA et al (2000) Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96(13):4075–4083PubMed Slovak ML, Kopecky KJ, Cassileth PA et al (2000) Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96(13):4075–4083PubMed
12.
go back to reference Yates J, Glidewell O, Wiernik P et al (1982) Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood 60(2):454–462PubMed Yates J, Glidewell O, Wiernik P et al (1982) Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood 60(2):454–462PubMed
13.
go back to reference Mayer RJ, Davis RB, Schiffer CA et al. (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 331(14):896–903 Mayer RJ, Davis RB, Schiffer CA et al. (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 331(14):896–903
14.
go back to reference Burnett AK, Russell NH, Hills RK et al (2013) Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML 15 trial. J Clin Oncol 31(27):3360–3368PubMed Burnett AK, Russell NH, Hills RK et al (2013) Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML 15 trial. J Clin Oncol 31(27):3360–3368PubMed
15.
go back to reference Medeiros BC (2018) Interpretation of clinical endpoints in trials of acute myeloid leukemia. Leuk Res 68:32–39PubMed Medeiros BC (2018) Interpretation of clinical endpoints in trials of acute myeloid leukemia. Leuk Res 68:32–39PubMed
16.
go back to reference Baek SJ, Kim KS, Nixon JB, Wilson LC, Eling TE (2001) Cyclooxygenase inhibitors regulate the expression of a TGF-β superfamily member that has proapoptotic and antitumorigenic activities. Mol Pharmacol 59(4):901–908PubMed Baek SJ, Kim KS, Nixon JB, Wilson LC, Eling TE (2001) Cyclooxygenase inhibitors regulate the expression of a TGF-β superfamily member that has proapoptotic and antitumorigenic activities. Mol Pharmacol 59(4):901–908PubMed
17.
go back to reference Liu T, Bauskin AR, Zaunders J et al (2003) Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells. Cancer Res 63(16):5034–5040PubMed Liu T, Bauskin AR, Zaunders J et al (2003) Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells. Cancer Res 63(16):5034–5040PubMed
18.
go back to reference Kadara H, Schroeder CP, Lotan D, Pisano C, Lotan R (2006) Induction of GDF-15/NAG-1/MIC-1 in human lung carcinoma cells by retinoid-related molecules and assessment of its role in apoptosis. Cancer Biol Ther 5(5):518–522PubMed Kadara H, Schroeder CP, Lotan D, Pisano C, Lotan R (2006) Induction of GDF-15/NAG-1/MIC-1 in human lung carcinoma cells by retinoid-related molecules and assessment of its role in apoptosis. Cancer Biol Ther 5(5):518–522PubMed
19.
go back to reference Brown DA, Breit SN, Buring J et al (2002) Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: A nested case-control study. Lancet 359:2159–2163PubMed Brown DA, Breit SN, Buring J et al (2002) Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: A nested case-control study. Lancet 359:2159–2163PubMed
20.
go back to reference Lankeit M, Kempf T, Dellas C et al (2008) Growth differentiation factor-15 for prognostic assessment of patients with acute pulmonary embolism. Am J Respir Crit Care Med 177:1018–1025PubMed Lankeit M, Kempf T, Dellas C et al (2008) Growth differentiation factor-15 for prognostic assessment of patients with acute pulmonary embolism. Am J Respir Crit Care Med 177:1018–1025PubMed
21.
go back to reference Brown DA, Moore J, Johnen H et al. (2007) Serum macrophage inhibitory cytokine 1 in rheumatoid arthritis. A potential marker of erosive joint destruction. Arthritis Rheum 56:753–764PubMed Brown DA, Moore J, Johnen H et al. (2007) Serum macrophage inhibitory cytokine 1 in rheumatoid arthritis. A potential marker of erosive joint destruction. Arthritis Rheum 56:753–764PubMed
22.
go back to reference Breit SN, Carrero JJ, Tsai VW et al (2012) Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease. Nephrol Dial Transplant 27:70–75PubMed Breit SN, Carrero JJ, Tsai VW et al (2012) Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease. Nephrol Dial Transplant 27:70–75PubMed
23.
go back to reference Tanno T, Bhanu NV, Oneal PA et al (2007) High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med 13:1096–1101PubMed Tanno T, Bhanu NV, Oneal PA et al (2007) High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med 13:1096–1101PubMed
24.
go back to reference Tamary H, Shalev H, Perez-Avraham G et al (2008) Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I. Blood 112:5241–5244PubMedPubMedCentral Tamary H, Shalev H, Perez-Avraham G et al (2008) Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I. Blood 112:5241–5244PubMedPubMedCentral
25.
go back to reference Ramirez JM, Schaad O, Durual S et al (2009) Growth differentiation factor 15 production is necessary for normal erythroid differentiation and is increased in refractory anaemia with ring-sideroblasts. Br J Haematol 144:251–262PubMed Ramirez JM, Schaad O, Durual S et al (2009) Growth differentiation factor 15 production is necessary for normal erythroid differentiation and is increased in refractory anaemia with ring-sideroblasts. Br J Haematol 144:251–262PubMed
26.
go back to reference Zhang L, Yang X, Pan H-Y et al (2009) Expression of growth differentiation factor 15 is positively correlated with histopathological malignant grade and in vitro cell proliferation in oral squamous cell carcinoma. Oral Oncol 5:627–632 Zhang L, Yang X, Pan H-Y et al (2009) Expression of growth differentiation factor 15 is positively correlated with histopathological malignant grade and in vitro cell proliferation in oral squamous cell carcinoma. Oral Oncol 5:627–632
27.
go back to reference Boyle GM, Pedley J, Martyn AC et al (2009) Macrophage inhibitory cytokine-1 is overexpressed in malignant melanoma and is associated with tumorigenicity. J Invest Dermatol 129:383–391PubMed Boyle GM, Pedley J, Martyn AC et al (2009) Macrophage inhibitory cytokine-1 is overexpressed in malignant melanoma and is associated with tumorigenicity. J Invest Dermatol 129:383–391PubMed
28.
go back to reference Hogendorf P, Durczyński A, Skulimowski A, Kumor A, Poznańska G, Strzelczyk J (2018) Growth differentiation factor (GDF-15) concentration combined with Ca125 levels in serum is superior to commonly used cancer biomarkers in differentiation of pancreatic mass. Cancer Biomark 21(3):505–511PubMed Hogendorf P, Durczyński A, Skulimowski A, Kumor A, Poznańska G, Strzelczyk J (2018) Growth differentiation factor (GDF-15) concentration combined with Ca125 levels in serum is superior to commonly used cancer biomarkers in differentiation of pancreatic mass. Cancer Biomark 21(3):505–511PubMed
29.
go back to reference Lima CA, Jammal MP, Martins-Filho A et al (2018) Stromal growth differentiation factor 15 and its association with ovarian cancer. Gynecol Obstet Invest 83(1):35–39PubMed Lima CA, Jammal MP, Martins-Filho A et al (2018) Stromal growth differentiation factor 15 and its association with ovarian cancer. Gynecol Obstet Invest 83(1):35–39PubMed
30.
go back to reference Moore AG, Brown DA, Fairlie WD et al (2000) The transforming growth factor-ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women. J Clin Endocrinol Metab 85:4781–4788PubMed Moore AG, Brown DA, Fairlie WD et al (2000) The transforming growth factor-ss superfamily cytokine macrophage inhibitory cytokine-1 is present in high concentrations in the serum of pregnant women. J Clin Endocrinol Metab 85:4781–4788PubMed
31.
go back to reference Segerer SE, Rieger L, Kapp M et al (2012) MIC-1 (a multifunctional modulator of dendritic cell phenotype and function) is produced by decidual stromal cells and trophoblasts. Hum Reprod 27(1):200–209PubMed Segerer SE, Rieger L, Kapp M et al (2012) MIC-1 (a multifunctional modulator of dendritic cell phenotype and function) is produced by decidual stromal cells and trophoblasts. Hum Reprod 27(1):200–209PubMed
32.
go back to reference Lu W, Wan Y, Li Z et al (2018) Growth differentiation factor 15 contributes to marrow adipocyte remodeling in response to the growth of leukemic cells. J Exp Clin Cancer Res 37(1):66PubMedPubMedCentral Lu W, Wan Y, Li Z et al (2018) Growth differentiation factor 15 contributes to marrow adipocyte remodeling in response to the growth of leukemic cells. J Exp Clin Cancer Res 37(1):66PubMedPubMedCentral
33.
go back to reference Zhai Y, Zhang J, Wang H et al (2016) Growth differentiation factor 15 contributes to cancer-associated fibroblasts-mediated chemo-protection of AML cells. J Exp Clin Cancer Res 35(1):147PubMedPubMedCentral Zhai Y, Zhang J, Wang H et al (2016) Growth differentiation factor 15 contributes to cancer-associated fibroblasts-mediated chemo-protection of AML cells. J Exp Clin Cancer Res 35(1):147PubMedPubMedCentral
34.
go back to reference Tarkun P, Mehtap O, Atesoglu EB, Geduk A, Musul MM, Hacihanefioglu A (2013) Serum hepcidin and growth differentiation factor-15 (GDF-15) levels in polycythemia vera and essential thrombocythemia. Eur J Haematol 91:228–235PubMed Tarkun P, Mehtap O, Atesoglu EB, Geduk A, Musul MM, Hacihanefioglu A (2013) Serum hepcidin and growth differentiation factor-15 (GDF-15) levels in polycythemia vera and essential thrombocythemia. Eur J Haematol 91:228–235PubMed
35.
go back to reference Zhao N, Yang J (2014) Expression of serum GDF15 and its clinical significance in multiple myeloma patients. Zhong Nan Da Xue Xue Bao Yi Xue Ban 39(3):270–275PubMed Zhao N, Yang J (2014) Expression of serum GDF15 and its clinical significance in multiple myeloma patients. Zhong Nan Da Xue Xue Bao Yi Xue Ban 39(3):270–275PubMed
36.
go back to reference Corre J, Hébraud B, Bourin P (2013) Concise review: growth differentiation factor 15 in pathology: a clinical role? Stem Cells Transl Med 2(12):946–952PubMedPubMedCentral Corre J, Hébraud B, Bourin P (2013) Concise review: growth differentiation factor 15 in pathology: a clinical role? Stem Cells Transl Med 2(12):946–952PubMedPubMedCentral
37.
go back to reference Corre J, Labat E, Espagnolle N et al (2012) Bioactivity of growth differentiation factor GDF15 secreted by bone marrow mesenchymal stem cells in multiple myeloma. Cancer Res 72(6):1395–1406PubMed Corre J, Labat E, Espagnolle N et al (2012) Bioactivity of growth differentiation factor GDF15 secreted by bone marrow mesenchymal stem cells in multiple myeloma. Cancer Res 72(6):1395–1406PubMed
38.
go back to reference Tarkun P, Birtas Atesoglu E, Mehtap O, Musul MM, Hacihanefioglu A (2014) Serum growth differentiation factor 15 levels in newly diagnosed multiple myeloma patients. Acta Haematol 131(3):173–178PubMed Tarkun P, Birtas Atesoglu E, Mehtap O, Musul MM, Hacihanefioglu A (2014) Serum growth differentiation factor 15 levels in newly diagnosed multiple myeloma patients. Acta Haematol 131(3):173–178PubMed
39.
go back to reference Li C, Wang X, Casal I et al (2016) Growth differentiation factor 15 is a promising diagnostic and prognostic biomarker in colorectal cancer. J Cell Mol Med 20(8):1420–1426PubMedPubMedCentral Li C, Wang X, Casal I et al (2016) Growth differentiation factor 15 is a promising diagnostic and prognostic biomarker in colorectal cancer. J Cell Mol Med 20(8):1420–1426PubMedPubMedCentral
40.
go back to reference Winand FJ, Boegemann M, Gallitz I et al (2014) GDF15 and Hepcidin as prognostic factors in patients with prostate cancer. J Mol Biomark Diagn 5:6 Winand FJ, Boegemann M, Gallitz I et al (2014) GDF15 and Hepcidin as prognostic factors in patients with prostate cancer. J Mol Biomark Diagn 5:6
41.
go back to reference Staff AC, Bock AJ, Becker C, Kempf T, Wollert KC, Davidson B (2010) Growth differentiation factor-15 as a prognostic biomarker in ovarian cancer. Gynecol Oncol 118(3):237–243PubMed Staff AC, Bock AJ, Becker C, Kempf T, Wollert KC, Davidson B (2010) Growth differentiation factor-15 as a prognostic biomarker in ovarian cancer. Gynecol Oncol 118(3):237–243PubMed
42.
go back to reference Lerner L, Hayes TG, Tao N et al (2015) Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients. J Cachexia Sarcopenia Muscle 6(4):317–324PubMedPubMedCentral Lerner L, Hayes TG, Tao N et al (2015) Plasma growth differentiation factor 15 is associated with weight loss and mortality in cancer patients. J Cachexia Sarcopenia Muscle 6(4):317–324PubMedPubMedCentral
Metadata
Title
Prognostic Impact of Serum Growth Differentiation Factor 15 Level in Acute Myeloid Leukemia Patients
Authors
Hany Mohamed Hegab
Amro Mohamed Sedky El-Ghammaz
Mostafa Kamal El-Razzaz
Reham Ali Ali Helal
Publication date
01-01-2021
Publisher
Springer India
Published in
Indian Journal of Hematology and Blood Transfusion / Issue 1/2021
Print ISSN: 0971-4502
Electronic ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-020-01315-7

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