Granulocyte colony stimulating factor increases drug resistance of leukaemic blast cells to daunorubicin.
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.
Márkász
László
L
Department of Paediatrics, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. markaszl@freemail.hu
Hajas
György
G
Kiss
Andrea
A
Lontay
Beáta
B
Rajnavölgyi
Eva
E
Erdodi
Ferenc
F
Oláh
Eva
E
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D003630:Daunorubicin / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D022423:Myeloid Cells / Q000187:drug effects* / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D003630:Daunorubicin