Wu Yong, Tan Ming, Chen Mei-Ling, Chen Yuan-Zhong
a Fujian Provincial Key Laboratory of Hematology , Fujian Institute of Hematology, Fujian Medical University Union Hospital , Fujian , P.R. China.
Hematology. 2018 Sep;23(8):439-447. doi: 10.1080/10245332.2018.1426540. Epub 2018 Jan 17.
We observed that ph + ALL patients administrated with recombinant human G-CSF (rhG-CSF) after intense chemotherapy have presented a trend of disease relapse. Thus, we aim to thoroughly investigate the expression and role of GM-CSFR and G-CSFR on ph + ALL patients.
SUP-B15, BALL-1 and primary leukemia cells were used in this study. Transcript levels were analyzed by quantitative PCR while cell viability was measured using a CCK-8 assay. Flow cytometry was used to assess the different stages of cell cycle.
We found that the mRNA expression levels of GM-CSFR and G-CSFR were higher in patients with ph + ALL, as well as in SUP-B15 cells. rhG-CSF was also observed to promote the viability of SUP-B15 cells while inversely inhibiting BALL-1 cell viability. In addition, we also determined that rhG-CSF (100 ng/ml) decreased the sensitivity of SUP-B15 cells to imatinib and nilotinib, while the results were exactly the contrary for dasatinib.
We demonstrated high expression levels of GM-CSFR and G-CSFR, as well as their promotable role for viability in ph + ALL cells. We further found that rhG-CSF influenced the sensitivity of SUP-B15 cells to TKIs.
我们观察到,接受强化化疗后的Ph+急性淋巴细胞白血病(ALL)患者使用重组人粒细胞集落刺激因子(rhG-CSF)后有疾病复发趋势。因此,我们旨在深入研究GM-CSFR和G-CSFR在Ph+ ALL患者中的表达及作用。
本研究使用SUP-B15、BALL-1和原发性白血病细胞。通过定量PCR分析转录水平,同时使用CCK-8法测量细胞活力。采用流式细胞术评估细胞周期的不同阶段。
我们发现,GM-CSFR和G-CSFR的mRNA表达水平在Ph+ ALL患者以及SUP-B15细胞中较高。还观察到rhG-CSF可促进SUP-B15细胞的活力,同时抑制BALL-1细胞的活力。此外,我们还确定rhG-CSF(100 ng/ml)降低了SUP-B15细胞对伊马替尼和尼洛替尼的敏感性,而达沙替尼的结果则相反。
我们证明了GM-CSFR和G-CSFR的高表达水平,以及它们在Ph+ ALL细胞中对活力的促进作用。我们还进一步发现rhG-CSF影响SUP-B15细胞对酪氨酸激酶抑制剂(TKIs)的敏感性。