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

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.

Ten-year Experiences on Initial Genetic Examination in Childhood Acute Lymphoblastic Leukaemia in Hungary (1993–2002). Technical Approaches and Clinical Implementation

“…In cases of trisomies or tetrasomies of the smallest chromosomes DNA-index was often lower than 1.16 indicating that flow cytometry alone is not reliable even for the detection of hyperdiploid B patients. Comparing the spectrum of supernumerary chromosomes in hyperdiploid B cases revealed by cytogenetic test and FISH a slight difference was found: by routine karyotyping trisomies of chromosomes 4,6,8,9,10,14,17,18,19,21, by FISH the involvement of 4, 6, 10, 12, 18, 21, and X chromosomes were detected most commonly. The difference can be explained by the use of different selected FISH probes and/or technical difficulties of chromosome analysis: misevaluation of extra chromosomes due to poor spreading of highly hyperdiploid metaphases [2,4,27].…”

The importance of the granulocyte-colony stimulating factor in oncology

“…Unfortunately, therapy with G-CSF involves some adverse events: in acute leukaemias it can increase drug resistance to daunorubicin [ 39 ]. In a study of Hershman et al the risk for developing myelodysplastic syndrome or acute myeloid leukemia for the patients with breast cancer treated with G-CSF was higher than for the ones not receiving it [ 40 ].…”