CORRELATION BETWEEN THE EXPRESSION OF ARGININOSUCCINATE
SYNTHETASE GENE AND DRUG RESISTANCE
MECHANISM OF CHRONIC MYELOGENOUS LEUKAEMIA
YUNXIA YIN1, JING NIE1*, YUANQIANG JIANG2
1West Hospital Pharmacy Department, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong,
250022, China
2Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214023, China
*corresponding author: niejing_sph@sohu.com
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Abstract:
Chronic myelogenous leukaemia (CML) induced by malignant clone of hematopoietic stem cell is usually treated with
imatinib mesylate. The treatment with imatinib has two main problems, first it cannot thoroughly eliminate leukaemia stem
cells and second it develops primary or secondary drug resistance. This study investigated whether the gene deletion of
argininosuccinate synthetase (ASS) was the reason for the drug resistance to CML and analysed their relationship as well as
the clinical effect of imatinib in treating CML. Bone marrow samples of CML patients were collected. Sample analysis was
performed using fluorescence in situ hybridization (FISH) of bone marrow cell. Fifteen out of one hundred patients with
CML were found to be lacking ASS gene, among which 11 patients received imatinib treatment. 10 of these patients were in
chronic phase and survived and one patient was in acceleration phase and survived. 40% (4 patients) from those in CP
registered disease progress and 1 patient from those in AP had progress. Among the 62 patients without the deletion of ASS
who received imatinib treatment, the disease condition of only 12.9% (8 patients) showed progress, suggesting that the
deletion of ASS gene could produce drug resistance in the treatment of chronic myelogenous leukaemia. It can be concluded
that, the deletion of ASS gene can affect the curative effect of imatinib in treating CML and can promote the progress of the
disease. Therefore, it can be used for evaluating the prognosis of patients.

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