Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.

Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.
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DOI:
10.1038/s41598-021-99147-6
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发表时间:
2021-10-04
期刊:
影响因子:
4.6
通讯作者:
Brown AL
Brown AL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Schraw JM;Woodhouse JP;Bernhardt MB;Taylor OA;Horton TM;Scheurer ME;Okcu MF;Rabin KR;Lupo PJ;Brown AL

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代谢组学可能揭示儿童急性淋巴细胞白血病(ALL)的治疗反应,然而,大多数评估都分析了骨髓或脑脊液(CSF),而不是在治疗的所有阶段收集。血液采集频繁,风险较低,但目前尚不清楚骨髓或CSF生物标志物研究的结果是否可以转化。我们使用液相色谱-质谱法分析了N = 10例B-ALL儿童的诱导终末血浆、骨髓和CSF。我们使用斯皮尔曼秩相关系数(rs)估计了在≥ 3例患者中检测到的血浆和骨髓/CSF代谢物丰度之间的相关性。在血浆中检测到大多数骨髓代谢物(N = 661; 81%),我们观察到中度至强相关性(中位数rs 0.62,四分位距[IQR] 0.29-0.83)。我们在血浆中检测到328种CSF代谢物(90%);血浆-CSF相关性较弱(中位数rs 0.37,IQR 0.07-0.70)。我们观察了终末诱导残留病相关途径中代谢物(丙酮酸、天冬酰胺)的血浆-骨髓相关性和疲劳生物标志物(γ-谷氨酰谷氨酰胺)的血浆-CSF相关性。血浆、骨髓和CSF代谢组之间存在相当大的重叠,我们观察到临床相关表型的生物标志物具有很强的相关性。血浆可能适合B-ALL的生物标志物研究。
Metabolomics may shed light on treatment response in childhood acute lymphoblastic leukemia (ALL), however, most assessments have analyzed bone marrow or cerebrospinal fluid (CSF), which are not collected during all phases of therapy. Blood is collected frequently and with fewer risks, but it is unclear whether findings from marrow or CSF biomarker studies may translate. We profiled end-induction plasma, marrow, and CSF from N = 10 children with B-ALL using liquid chromatography-mass spectrometry. We estimated correlations between plasma and marrow/CSF metabolite abundances detected in ≥ 3 patients using Spearman rank correlation coefficients (rs). Most marrow metabolites were detected in plasma (N = 661; 81%), and we observed moderate-to-strong correlations (median rs 0.62, interquartile range [IQR] 0.29–0.83). We detected 328 CSF metabolites in plasma (90%); plasma-CSF correlations were weaker (median rs 0.37, IQR 0.07–0.70). We observed plasma-marrow correlations for metabolites in pathways associated with end-induction residual disease (pyruvate, asparagine) and plasma-CSF correlations for a biomarker of fatigue (gamma-glutamylglutamine). There is considerable overlap between the plasma, marrow, and CSF metabolomes, and we observed strong correlations for biomarkers of clinically relevant phenotypes. Plasma may be suitable for biomarker studies in B-ALL.
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