[Influence of IFN-alpha and IFN-alpha combined with GM-CSF on expression of the genes related to cell apoptosis of MNCs from bone marrow in CML patients].
OBJECTIVE
To investigate the effects of interferon-alpha(IFN-alpha) and IFN-alpha combined with granulocytic macrophage colony-stimulating factor(GM-CSF) on expression of bcr-abl, bcl-2 and c-myc genes in the mononuclear cells(MNCs) from bone marrow(BM) of the patients with chronic myelogenous leukemia at chronic phase(CML-CP).


METHODS
The MNCs were collected from bone marrow of 14 CML-CP patients by centrifugalization in lymphocyte-separation medium, and cultivated in the medium with IFN-alpha and IFN-alpha plus GM-CSF for 24 hours. The expression levels of bcr-abl, bcl-2, c-myc and beta-actin were detected by using relatively quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and optical density scanning technology for the amplified fragments. The statistical differences between each inducing experimental group and the control were analyzed by t-test in pairs.


RESULTS
Both IFN-alpha (200 U.ml-1) and IFN-alpha combined with GM-CSF (10 ng.ml-1) significantly inhibited bcr-abl gene expression, meanwhile IFN-alpha partially suppressed c-myc and bcl-2 gene expression, and GM-CSF significantly inhibited bcl-2 gene expression but partially upregulated bcr-abl and c-myc gene expression levels on the basis of IFN-alpha effects.


CONCLUSIONS
Both IFN-alpha and IFN-alpha plus GM-CSF can inhibit the expression of anti-apoptosis gene such as bcr-abl and bcl-2, and regulate the expression of c-myc. It is the possible mechanism of IFN-alpha therapy or combined therapy on CML at chronic phase that the malignant clone expansion is inhibited by promoting apoptotic cell death.
Tang
L J
LJ
Research Center for Molecular Biology, Hunan Medical University, Changsha 410078.
Chen
H C
HC
Peng
X H
XH
D001854:Bone Marrow Cells / Q000473:pathology; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis* / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016044:Fusion Proteins, bcr-abl