CD69以及CD24在CML細胞中對於細胞生長及細胞分化所扮演的角色

慢性骨髓性白血病(chronic myeloid leukemia, CML)，是種造血幹細胞惡性增生的癌症。在多數的CML患者身上找到一種不正常的染色體，稱之為費城染色體 (Philadelphia Chromosome)。是由第9對染色體上的Abelson leukemia virus (Abl)和第22對染色體的Breakpoint cluster region (Bcr)互相轉位而形成，進一步產生了Bcr-Abl fusion gene。Bcr-Abl是持續活化態的tyrosine kinase (TK)，可造成cell transformation、proliferation、differentiation以及抑制apoptosis。在本實驗室過去的研究證實，CD69和CD24為Bcr-Abl下游所調控的蛋白。CD69是一個已知的early lymphocyte activation marker，是T cell或B cell早期的活化抗原；而CD24則會參與在細胞的黏附以及腫瘤生成的過程中。在本篇研究中證明，在K562細胞中，利用大量表現CD69或CD24的穩定細胞株可部分抑制STI571所誘導的紅血球分化以及細胞凋亡。另外，大量表現CD24穩定細胞株可部分回復STI571所抑制的細胞生長。CD69會減少STI571所誘導的G1 arrest，但此結果並未發現於大量表現CD24的穩定細胞株中。相同的，當我們利用siRNA knockdown CD69或CD24表現後，可以增加STI571所誘導的紅血球分化和細胞凋亡。另外，當knockdown CD69後可增加細胞停滯於STI571所誘導的G1 arrest。除此之外，我們發現當抑制CD69或CD24表現後，同時會降低造血幹細胞標記(stem cell marker)的mRNA表現量。根據以上實驗結果，證明CD69或CD24參與Bcr-Abl訊號傳遞，可促進細胞的增生以及抑制細胞凋亡和分化，並且可能參與維持CML細胞於造血幹細胞的狀態。

關鍵字

慢性骨隨性白血病；細胞分化； CD69 ； CD24

並列摘要

Bcr-Abl protein is a constitutively active tyrosine kinase which is encoded by Philadelphia chromosome in chronic myeloid leukemia (CML). Bcr-Abl induces cell transformation, proliferation, differentiation and apoptosis inhibition in CML cells. Our previous studies have demonstrated that CD69 and CD24 are downstream targets of Bcr-Abl signaling. CD69 is an early activation antigen of lymphocytes. CD24 is involved in cell adhesion and tumorgenesis. In this study, we show that CD69 or CD24 overexpression partially inhibited STI571-induced erythroid differentiation and apoptosis in CML cell line K562. CD24 overexpression partially reversed STI571- inhibited cell proliferation in K562 cells. CD69 inhibited STI571-mediated G1 arrest in K562 cells but not CD24. Similarly, down-regulation of CD69 or CD24 by siRNAs also enhanced STI571-induced erythroid differentiation and apoptosis. The siRNA knockdown of CD69 enhanced STI571-mediated G1 arrest in K562 cells, but not the siRNA knockdown of CD24. In addition, CD69 or CD24 knockdown significantly reduced the mRNA levels of hematopoietic stem cell (HSC) markers. Taken together, these results suggested that CD69 and CD24 regulate the induction of cell proliferation, the inhibition of apoptosis, and cells differentiation, as well as the maintenance of HSC status of CML cells in Bcr-Abl signaling.

並列關鍵字

CML ； cell differentiation ； CD69 ； CD24

參考文獻

Aigner S, Ruppert M, Hubbe M, et al. Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin. Int Immunol. 7(10):1557-65, 1995.

Baumann P, Cremers N, Kroese F, et al. CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis. Cancer Res. 65(23):10783-93, 2005.

Bezouska K, Snajdrová R, Krenek K, et al. Carboxylated calixarenes bind strongly to CD69 and protect CD69(+) killer cells from suicidal cell death induced by tumor cell surface ligands. Bioorg Med Chem. 18(4):1434-40, 2010.

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Choi D, Lee HW, Hur KY, et al. Cancer stem cell markers CD133 and CD24 correlate with invasiveness and differentiation in colorectal adenocarcinoma. World J Gastroenterol. 15(18):2258-64, 2009.

國際替代計量

CD69以及CD24在CML細胞中對於細胞生長及細胞分化所扮演的角色

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