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Published in: Pathology & Oncology Research 3/2008

01-09-2008 | Original Paper

Granulocyte Colony Stimulating Factor Increases Drug Resistance of Leukaemic Blast Cells to Daunorubicin

Authors: László Márkász, György Hajas, Andrea Kiss, Beáta Lontay, Éva Rajnavölgyi, Ferenc Erdődi, Éva Oláh

Published in: Pathology & Oncology Research | Issue 3/2008

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Abstract

Acute leukaemia is known as the most common cancer in childhood. Febrile neutropenia is a common serious side effect of the cytostatic treatment of malignancies. The clinical use of Granulocyte Colony Stimulating Factor (G-CSF) has become widespread to minimize chemotherapy-induced myelosuppression and febrile neutropenia in childhood solid tumors, acute lymphoid leukaemia (ALL) and in several trials with AML. In case of ALL this seems to be reasonable because, due to the absence of G-CSF receptor (G-CSFR) on the surface of normal lymphoid cells, G-CSF does not have any influence on the pathways of proliferation and differentiation of lymphoid lineage cells. It has been suggested, however, that ALL blasts with B or T cell surface antigens as well as biphenotypic leukaemia cells express G-CSFR, and they are able to respond to exogenously added G-CSF with proliferation. In this study we investigated how G-CSF might influence the sensitivity of leukemic cells to daunorubicin induced cell death using MTT assay, flow cytometry and Western blot analysis. After pretreatment of KG-1 leukaemic cells with G-CSF a moderate increase in the resistance of these cells to daunorubicin could be observed. These results draw attention to the risk of G-CSF application as an adjuvant therapy of childhood ALL. In addition, adjuvant treatment of AML patients with G-CSF in order to prevent neutropenia, or its use in priming regimens might result resistance to daunorubicin.
Literature
1.
go back to reference Licht JD, Sternberg DW (2005) The molecular pathology of acute myeloid leukemia. Hematology 2005:137–142CrossRef Licht JD, Sternberg DW (2005) The molecular pathology of acute myeloid leukemia. Hematology 2005:137–142CrossRef
2.
go back to reference Kager L, Evans WE (2006) Pharmacogenomics of acute lymphoblastic leukemia. Curr Opin Hematol 13(4):260–265CrossRefPubMed Kager L, Evans WE (2006) Pharmacogenomics of acute lymphoblastic leukemia. Curr Opin Hematol 13(4):260–265CrossRefPubMed
3.
go back to reference Woods WG (2006) Curing childhood acute myeloid leukemia (AML) at the half-way point: promises to keep and miles to go before we sleep. Pediatr Blood Cancer 46(5):565–569CrossRefPubMed Woods WG (2006) Curing childhood acute myeloid leukemia (AML) at the half-way point: promises to keep and miles to go before we sleep. Pediatr Blood Cancer 46(5):565–569CrossRefPubMed
4.
go back to reference Sasse EC, Sasse AD, Brandalise S et al (2005) Colony stimulating factors for prevention of myelosupressive therapy induced febrile neutropenia in children with acute lymphoblastic leukaemia. Cochrane Database Syst Rev 3:CD004139PubMed Sasse EC, Sasse AD, Brandalise S et al (2005) Colony stimulating factors for prevention of myelosupressive therapy induced febrile neutropenia in children with acute lymphoblastic leukaemia. Cochrane Database Syst Rev 3:CD004139PubMed
5.
go back to reference Timmer-Bonte JN, Tjan-Heijnen VC (2006) Febrile neutropenia: highlighting the role of prophylactic antibiotics and granulocyte colony-stimulating factor during standard dose chemotherapy for solid tumors. Anticancer Drugs 17(8):881–889CrossRefPubMed Timmer-Bonte JN, Tjan-Heijnen VC (2006) Febrile neutropenia: highlighting the role of prophylactic antibiotics and granulocyte colony-stimulating factor during standard dose chemotherapy for solid tumors. Anticancer Drugs 17(8):881–889CrossRefPubMed
6.
go back to reference Heath JA, Steinherz PG, Altman A et al (2003) Human granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia: a Children’s Cancer Group Study. J Clin Oncol 21(8):1612–1617CrossRefPubMed Heath JA, Steinherz PG, Altman A et al (2003) Human granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia: a Children’s Cancer Group Study. J Clin Oncol 21(8):1612–1617CrossRefPubMed
7.
go back to reference Lehrnbecher T, Zimmermann M, Reinhardt D et al (2007) Prophylactic human granulocyte colony-stimulating factor after induction therapy in pediatric acute myeloid leukemia. Blood 109(3):936–943CrossRefPubMed Lehrnbecher T, Zimmermann M, Reinhardt D et al (2007) Prophylactic human granulocyte colony-stimulating factor after induction therapy in pediatric acute myeloid leukemia. Blood 109(3):936–943CrossRefPubMed
8.
go back to reference Sachs L (1996) The control of hematopoiesis and leukemia: from basic biology to the clinic. Proc Natl Acad Sci U S A 93(10):4742–4749CrossRefPubMed Sachs L (1996) The control of hematopoiesis and leukemia: from basic biology to the clinic. Proc Natl Acad Sci U S A 93(10):4742–4749CrossRefPubMed
9.
go back to reference Lopez AF, Williamson DJ, Gamble JR et al (1986) Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival. J Clin Invest 78(5):1220–1228CrossRefPubMed Lopez AF, Williamson DJ, Gamble JR et al (1986) Recombinant human granulocyte-macrophage colony-stimulating factor stimulates in vitro mature human neutrophil and eosinophil function, surface receptor expression, and survival. J Clin Invest 78(5):1220–1228CrossRefPubMed
10.
go back to reference Dempke W, Von Poblozki A, Grothey A et al (2000) Human hematopoietic growth factors: old lessons and new perspectives. Anticancer Res 20(6D):5155–5164PubMed Dempke W, Von Poblozki A, Grothey A et al (2000) Human hematopoietic growth factors: old lessons and new perspectives. Anticancer Res 20(6D):5155–5164PubMed
11.
go back to reference Frampton JE, Keating GM (2005) Spotlight on pegfilgrastim in chemotherapy-induced neutropenia. BioDrugs 19(6):405–407CrossRefPubMed Frampton JE, Keating GM (2005) Spotlight on pegfilgrastim in chemotherapy-induced neutropenia. BioDrugs 19(6):405–407CrossRefPubMed
12.
go back to reference Ravandi F (2006) Role of cytokines in the treatment of acute leukemias: a review. Leukemia 20(4):563–571CrossRefPubMed Ravandi F (2006) Role of cytokines in the treatment of acute leukemias: a review. Leukemia 20(4):563–571CrossRefPubMed
13.
go back to reference Asano S (1991) Human granulocyte colony-stimulating factor: its basic aspects and clinical applications. Am J Pediatr Hematol Oncol 13(4):400–413CrossRefPubMed Asano S (1991) Human granulocyte colony-stimulating factor: its basic aspects and clinical applications. Am J Pediatr Hematol Oncol 13(4):400–413CrossRefPubMed
14.
go back to reference Nicholson SE, Novak U, Ziegler SF et al (1995) Distinct regions of the granulocyte colony-stimulating factor receptor are required for tyrosine phosphorylation of the signaling molecules JAK2, Stat3, and p42, p44MAPK. Blood 86(10):3698–3704PubMed Nicholson SE, Novak U, Ziegler SF et al (1995) Distinct regions of the granulocyte colony-stimulating factor receptor are required for tyrosine phosphorylation of the signaling molecules JAK2, Stat3, and p42, p44MAPK. Blood 86(10):3698–3704PubMed
15.
go back to reference Fukunaga R, Seto Y, Mizushima S et al (1990) Three different mRNAs encoding human granulocyte colony-stimulating factor receptor. Proc Natl Acad Sci U S A 87(22):8702–8706CrossRefPubMed Fukunaga R, Seto Y, Mizushima S et al (1990) Three different mRNAs encoding human granulocyte colony-stimulating factor receptor. Proc Natl Acad Sci U S A 87(22):8702–8706CrossRefPubMed
16.
go back to reference Glaspy JA, Golde DW (1992) Granulocyte colony-stimulating factor (G-CSF): preclinical and clinical studies. Semin Oncol 19(4):386–394PubMed Glaspy JA, Golde DW (1992) Granulocyte colony-stimulating factor (G-CSF): preclinical and clinical studies. Semin Oncol 19(4):386–394PubMed
17.
go back to reference Dombret H (1996) Granulocytic colony-stimulating factors in the management of patients with acute myeloid leukemia. Hematol Cell Ther 38(3):231–240CrossRefPubMed Dombret H (1996) Granulocytic colony-stimulating factors in the management of patients with acute myeloid leukemia. Hematol Cell Ther 38(3):231–240CrossRefPubMed
18.
go back to reference Becker PS (2004) Growth factor priming in therapy of acute myelogenous leukemia. Curr Hematol Rep 3(6):413–418PubMed Becker PS (2004) Growth factor priming in therapy of acute myelogenous leukemia. Curr Hematol Rep 3(6):413–418PubMed
19.
go back to reference Hubeek I, Litvinova E, Peters GJ et al (2004) The effect of G-CSF on the in vitro cytotoxicity of cytarabine and fludarabine in the FLAG combination in pediatric acute myeloid leukemia. Int J Oncol 25(6):1823–1829PubMed Hubeek I, Litvinova E, Peters GJ et al (2004) The effect of G-CSF on the in vitro cytotoxicity of cytarabine and fludarabine in the FLAG combination in pediatric acute myeloid leukemia. Int J Oncol 25(6):1823–1829PubMed
20.
go back to reference Buchner T, Hiddemann W, Wormann B et al (1997) Hematopoietic growth factors in acute myeloid leukemia: supportive and priming effects. Semin Oncol 24(1):124–131PubMed Buchner T, Hiddemann W, Wormann B et al (1997) Hematopoietic growth factors in acute myeloid leukemia: supportive and priming effects. Semin Oncol 24(1):124–131PubMed
21.
go back to reference Nicola NA, Metcalf D (1985) Binding of 125I-labeled granulocyte colony-stimulating factor to normal murine hemopoietic cells. J Cell Physiol 124(2):313–321CrossRefPubMed Nicola NA, Metcalf D (1985) Binding of 125I-labeled granulocyte colony-stimulating factor to normal murine hemopoietic cells. J Cell Physiol 124(2):313–321CrossRefPubMed
22.
go back to reference Liu WM, Powles T, Shamash J et al (2004) Effect of haemopoietic growth factors on cancer cell lines and their role in chemosensitivity. Oncogene 23(4):981–990CrossRefPubMed Liu WM, Powles T, Shamash J et al (2004) Effect of haemopoietic growth factors on cancer cell lines and their role in chemosensitivity. Oncogene 23(4):981–990CrossRefPubMed
23.
go back to reference Handa A, Kashimura T, Takeuchi S et al (2000) Expression of functional granulocyte colony-stimulating factor receptors on human B-lymphocytic leukemia cells. Ann Hematol 79(3):127–131CrossRefPubMed Handa A, Kashimura T, Takeuchi S et al (2000) Expression of functional granulocyte colony-stimulating factor receptors on human B-lymphocytic leukemia cells. Ann Hematol 79(3):127–131CrossRefPubMed
24.
go back to reference Kita K, Nishii K, Ohishi K et al (1993) Frequent gene expression of granulocyte colony-stimulating factor (G-CSF) receptor in CD7+ surface CD3− acute lymphoblastic leukaemia. Leukemia 7(8):1184–1190PubMed Kita K, Nishii K, Ohishi K et al (1993) Frequent gene expression of granulocyte colony-stimulating factor (G-CSF) receptor in CD7+ surface CD3− acute lymphoblastic leukaemia. Leukemia 7(8):1184–1190PubMed
25.
go back to reference Shimoda K, Okamura S, Harada N et al (1992) Detection of the granulocyte colony-stimulating factor receptor using biotinylated granulocyte colony-stimulating factor: presence of granulocyte colony-stimulating factor receptor on CD34-positive hematopoietic progenitor cells. Res Exp Med (Berl) 192(4):245–255CrossRef Shimoda K, Okamura S, Harada N et al (1992) Detection of the granulocyte colony-stimulating factor receptor using biotinylated granulocyte colony-stimulating factor: presence of granulocyte colony-stimulating factor receptor on CD34-positive hematopoietic progenitor cells. Res Exp Med (Berl) 192(4):245–255CrossRef
26.
go back to reference Inukai T, Sugita K, Iijima K et al (1998) Leukemic cells with 11q23 translocations express granulocyte colony-stimulating factor (G-CSF) receptor and their proliferation is stimulated with G-CSF. Leukemia 12(3):382–389CrossRefPubMed Inukai T, Sugita K, Iijima K et al (1998) Leukemic cells with 11q23 translocations express granulocyte colony-stimulating factor (G-CSF) receptor and their proliferation is stimulated with G-CSF. Leukemia 12(3):382–389CrossRefPubMed
27.
go back to reference Benko I, Kovacs P, Szegedi I et al (2001) Effect of myelopoietic and pleiotropic cytokines on colony formation by blast cells of children with acute lymphoblastic leukemia. Naunyn Schmiedebergs Arch Pharmacol 363(5):499–508CrossRefPubMed Benko I, Kovacs P, Szegedi I et al (2001) Effect of myelopoietic and pleiotropic cytokines on colony formation by blast cells of children with acute lymphoblastic leukemia. Naunyn Schmiedebergs Arch Pharmacol 363(5):499–508CrossRefPubMed
28.
go back to reference Higashigawa M, Kuwabara H, Cao DC et al (1996) Heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C cytotoxicity in childhood leukemias which express myeloid markers. Leuk Lymphoma 22(3–4):279–285PubMedCrossRef Higashigawa M, Kuwabara H, Cao DC et al (1996) Heterogeneous effects of G-CSF and GM-CSF on cell growth and ara-C cytotoxicity in childhood leukemias which express myeloid markers. Leuk Lymphoma 22(3–4):279–285PubMedCrossRef
29.
go back to reference de Lau WB, Hurenkamp J, Berendes P et al (1998) The gene encoding the granulocyte colony-stimulating factor receptor is a target for deregulation in pre-B ALL by the t(1;19)-specific oncoprotein E2A-Pbx1. Oncogene 17(4):503–510CrossRefPubMed de Lau WB, Hurenkamp J, Berendes P et al (1998) The gene encoding the granulocyte colony-stimulating factor receptor is a target for deregulation in pre-B ALL by the t(1;19)-specific oncoprotein E2A-Pbx1. Oncogene 17(4):503–510CrossRefPubMed
30.
go back to reference Williams DL, Look AT, Melvin SL et al (1984) New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia. Cell 36(1):101–109CrossRefPubMed Williams DL, Look AT, Melvin SL et al (1984) New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia. Cell 36(1):101–109CrossRefPubMed
31.
go back to reference Matsushita K, Arima N, Ohtsubo H et al (1997) Granulocyte-colony stimulating factor-induced proliferation of primary adult T-cell leukaemia cells. Br J Haematol 96(4):715–723CrossRefPubMed Matsushita K, Arima N, Ohtsubo H et al (1997) Granulocyte-colony stimulating factor-induced proliferation of primary adult T-cell leukaemia cells. Br J Haematol 96(4):715–723CrossRefPubMed
32.
go back to reference Oh EJ, Kahng J, Kim Y et al (2003) Expression of functional markers in acute lymphoblastic leukemia. Leuk Res 27(10):903–908CrossRefPubMed Oh EJ, Kahng J, Kim Y et al (2003) Expression of functional markers in acute lymphoblastic leukemia. Leuk Res 27(10):903–908CrossRefPubMed
33.
go back to reference Koeffler HP, Golde DW (1980) Human myeloid leukemia cell lines: a review. Blood 56(3):344–350PubMed Koeffler HP, Golde DW (1980) Human myeloid leukemia cell lines: a review. Blood 56(3):344–350PubMed
34.
go back to reference Minotti G, Menna P, Salvatorelli E et al (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 56(2):185–229CrossRefPubMed Minotti G, Menna P, Salvatorelli E et al (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 56(2):185–229CrossRefPubMed
35.
go back to reference Ravindranath Y (2003) Recent advances in pediatric acute lymphoblastic and myeloid leukemia. Curr Opin Oncol 15(1):23–35CrossRefPubMed Ravindranath Y (2003) Recent advances in pediatric acute lymphoblastic and myeloid leukemia. Curr Opin Oncol 15(1):23–35CrossRefPubMed
36.
go back to reference Tallman MS, Gilliland DG, Rowe JM (2005) Drug therapy for acute myeloid leukemia. Blood 106(4):1154–1163CrossRefPubMed Tallman MS, Gilliland DG, Rowe JM (2005) Drug therapy for acute myeloid leukemia. Blood 106(4):1154–1163CrossRefPubMed
37.
go back to reference Hajas G, Zsiros E, Laszlo T et al (2004) New phenotypic, functional and electrophysiological characteristics of KG-1 cells. Immunol Lett 92(1–2):97–106CrossRefPubMed Hajas G, Zsiros E, Laszlo T et al (2004) New phenotypic, functional and electrophysiological characteristics of KG-1 cells. Immunol Lett 92(1–2):97–106CrossRefPubMed
38.
go back to reference Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259):680–685CrossRefPubMed Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259):680–685CrossRefPubMed
39.
go back to reference Muranyi A, Erdodi F, Ito M et al (1998) Identification and localization of myosin phosphatase in human platelets. Biochem J 330(Pt 1):225–231PubMed Muranyi A, Erdodi F, Ito M et al (1998) Identification and localization of myosin phosphatase in human platelets. Biochem J 330(Pt 1):225–231PubMed
40.
go back to reference Miyauchi J, Kelleher CA, Yang YC et al (1987) The effects of three recombinant growth factors, IL-3, GM-CSF, and G-CSF, on the blast cells of acute myeloblastic leukemia maintained in short-term suspension culture. Blood 70(3):657–663PubMed Miyauchi J, Kelleher CA, Yang YC et al (1987) The effects of three recombinant growth factors, IL-3, GM-CSF, and G-CSF, on the blast cells of acute myeloblastic leukemia maintained in short-term suspension culture. Blood 70(3):657–663PubMed
41.
go back to reference Delwel R, Salem M, Pellens C et al (1988) Growth regulation of human acute myeloid leukemia: effects of five recombinant hematopoietic factors in a serum-free culture system. Blood 72(6):1944–1949PubMed Delwel R, Salem M, Pellens C et al (1988) Growth regulation of human acute myeloid leukemia: effects of five recombinant hematopoietic factors in a serum-free culture system. Blood 72(6):1944–1949PubMed
42.
go back to reference Vellenga E, Ostapovicz D, O’Rourke B et al (1987) Effects of recombinant IL-3, GM-CSF, and G-CSF on proliferation of leukemic clonogenic cells in short-term and long-term cultures. Leukemia 1(8):584–589PubMed Vellenga E, Ostapovicz D, O’Rourke B et al (1987) Effects of recombinant IL-3, GM-CSF, and G-CSF on proliferation of leukemic clonogenic cells in short-term and long-term cultures. Leukemia 1(8):584–589PubMed
43.
go back to reference Litvinova E, Gurova K, Chimishkian K et al (1999) Effects of CSFS and their combinations with chemotherapeutic agents (CH) on leukemic blasts (LB) in children (MTT-assay). Adv Exp Med Biol 457:585–592PubMed Litvinova E, Gurova K, Chimishkian K et al (1999) Effects of CSFS and their combinations with chemotherapeutic agents (CH) on leukemic blasts (LB) in children (MTT-assay). Adv Exp Med Biol 457:585–592PubMed
44.
go back to reference van der Kolk DM, de Vries EG, Muller M et al (2002) The role of drug efflux pumps in acute myeloid leukemia. Leuk Lymphoma 43(4):685–701CrossRefPubMed van der Kolk DM, de Vries EG, Muller M et al (2002) The role of drug efflux pumps in acute myeloid leukemia. Leuk Lymphoma 43(4):685–701CrossRefPubMed
45.
go back to reference Miranda MB, Xu H, Torchia JA et al (2005) Cytokine-induced myeloid differentiation is dependent on activation of the MEK/ERK pathway. Leuk Res 29(11):1293–1306CrossRefPubMed Miranda MB, Xu H, Torchia JA et al (2005) Cytokine-induced myeloid differentiation is dependent on activation of the MEK/ERK pathway. Leuk Res 29(11):1293–1306CrossRefPubMed
46.
go back to reference Prieto J, Eklund A, Patarroyo M (1994) Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages. Cell Immunol 156(1):191–211CrossRefPubMed Prieto J, Eklund A, Patarroyo M (1994) Regulated expression of integrins and other adhesion molecules during differentiation of monocytes into macrophages. Cell Immunol 156(1):191–211CrossRefPubMed
47.
48.
go back to reference Larson RS, Springer TA (1990) Structure and function of leukocyte integrins. Immunol Rev 114:181–217CrossRefPubMed Larson RS, Springer TA (1990) Structure and function of leukocyte integrins. Immunol Rev 114:181–217CrossRefPubMed
49.
go back to reference Inghirami G, Grignani F, Sternas L et al (1990) Down-regulation of LFA-1 adhesion receptors by C-myc oncogene in human B lymphoblastoid cells. Science 250(4981):682–686CrossRefPubMed Inghirami G, Grignani F, Sternas L et al (1990) Down-regulation of LFA-1 adhesion receptors by C-myc oncogene in human B lymphoblastoid cells. Science 250(4981):682–686CrossRefPubMed
50.
go back to reference Bashey A, Healy L, Marshall CJ (1994) Proliferative but not nonproliferative responses to granulocyte colony-stimulating factor are associated with rapid activation of the p21ras/MAP kinase signalling pathway. Blood 83(4):949–957PubMed Bashey A, Healy L, Marshall CJ (1994) Proliferative but not nonproliferative responses to granulocyte colony-stimulating factor are associated with rapid activation of the p21ras/MAP kinase signalling pathway. Blood 83(4):949–957PubMed
Metadata
Title
Granulocyte Colony Stimulating Factor Increases Drug Resistance of Leukaemic Blast Cells to Daunorubicin
Authors
László Márkász
György Hajas
Andrea Kiss
Beáta Lontay
Éva Rajnavölgyi
Ferenc Erdődi
Éva Oláh
Publication date
01-09-2008
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 3/2008
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-008-9057-5

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