脾酪氨酸激酶酪氨酸 348 位的磷酸化（pSyk³⁴⁸）可能是慢性髓细胞白血病（CML）晚期的一个标志物。

Phosphorylation of spleen tyrosine kinase at tyrosine 348 (pSyk³⁴⁸) may be a marker of advanced phase of Chronic Myeloid Leukemia (CML).

机构信息

Hématologie Biologique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.

Hématologie Clinique, CHU Estaing, 1 Place Lucie Aubrac, 63003 Clermont-Ferrand Cedex 1, France.

出版信息

Leuk Res. 2015 Mar;39(3):329-34. doi: 10.1016/j.leukres.2014.11.014. Epub 2014 Dec 13.

DOI:10.1016/j.leukres.2014.11.014

PMID:25612940

Abstract

We investigated Syk as a potential marker of CML progression. We observed a significant over-expression of Syk mRNA and constitutive phosphorylation of Syk Y348 in blast cells from six AP or BP-CML, but not in 15 CML in chronic phase. We could follow in vivo the recurrence of pSyk(348) throughout blast cell escape, despite observing storage of dasatinib in blast cells. A combination of dasatinib and R406 did not improve therapeutic efficacy in vitro. Our results strongly suggest that Syk activation could be a relevant biomarker of disease progression and dasatinib resistance but is probably not a molecular target.

摘要

我们研究了 Syk 是否为 CML 进展的潜在标志物。我们观察到，6 例加速期或急变期 AP/BC-CML 的原始细胞中，Syk mRNA 过度表达，Syk Y348 持续磷酸化，但在 15 例慢性期 CML 中并未观察到。尽管我们观察到 dasatinib 在原始细胞中储存，但在原始细胞逃避过程中，我们可以跟踪 pSyk(348) 的重现。尽管体外联合使用 dasatinib 和 R406 并没有提高治疗效果。我们的研究结果强烈表明，Syk 激活可能是疾病进展和 dasatinib 耐药的相关生物标志物，但可能不是一个分子靶点。