Label-Free Identification of AML1-ETO Positive Acute Myeloid Leukemia Using Single-Cell Raman Spectroscopy

Author:

Wang Yang1,Wang Yimeng2,Chen Xing3456,Zhu Mingyao3456,Xu Yang3,Wu Yihui3456ORCID,Gao Sujun7,Zhang Ming7,Su Long7,Han Wei7,Chi Mingbo3456ORCID

Affiliation:

1. Changchun Sci-Tech University, Shuangyang, Jilin Province, China

2. National Science Library (Chengdu), Chinese Academy of Sciences, Chengdu, China

3. Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun, Jilin, China

4. University of Chinese Academy of Sciences, Beijing, China

5. State Key Laboratory of Applied Optics, Changchun, Jilin, China

6. Key Laboratory of Optical System Advanced Manufacturing Technology, Chinese Academy of Sciences, Changchun, Jilin, China

7. Department of Hematology, The First Bethune Hospital, Jilin University, Changchun, China

Abstract

Acute myeloid leukemia (AML) is a malignant hematological tumor disease. Chromosomal abnormality is an independent prognostic factor in AML. AML with t(8:21) (q22; q22)/AML1-ETO (AE) is an independent disease group. In this research, a new method based on Raman spectroscopy is reported for label-free single-cell identification and analysis of AE fusion genes in clinical AML patients. Raman spectroscopy reflects the intrinsic vibration information of molecules in a label-free and non-destructive manner, and the fingerprint Raman spectrum of cells characterizes intracellular molecular types and relative concentration information, so as to realize the identification and molecular metabolism analysis of different kinds of cells. We collected the Raman spectra of bone marrow cells from clinically diagnosed AML M2 patients with and without the AE fusion gene. Through comparison of the average spectra and identification analysis based on multivariate statistical methods such as principal component analysis and linear discriminant analysis, the distinction between AE positive and negative sample cells in M2 AML patients was successfully achieved, and the single-cell identification accuracy was more than 90%. At the same time, the Raman spectra of the two types of cells were analyzed by the multivariate curve resolution alternating least squares decomposition method. It was found that the presence of the AE fusion gene may lead to the metabolic changes of lipid and nucleic acid in AML cells, which was consistent with the results of genomic and metabolomic multi-omics studies. The above results indicate that single-cell Raman spectroscopy has the potential for early identification of AE-positive AML.

Funder

National Natural Science Foundation of China

the Youth Innovation Promotion Association CAS

Publisher

SAGE Publications

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