Serum 2-Hydroxyglutarate Level Is a Prognostic Marker in Acute Myeloid Leukemia-Reference-Cited by-全球学者库

Serum 2-Hydroxyglutarate Level Is a Prognostic Marker in Acute Myeloid Leukemia

Published:2012-11-16 Issue:21 Volume:120 Page:1433-1433
ISSN:0006-4971
Container-title:Blood
language:en
Short-container-title:

Author:

Wang Jing-Han¹,Chen Wen-Lian¹,Chen Tian-Lu²,Zhu Yong-Mei¹,Zhang Wei-Na³,Li Yang¹,Wu Song-Fang²,Qiu Yun-Ping²,Zhao Ai-Hua²,Li Jun-Min¹,Mi Jian-qing¹,Jin Jie⁴,Wang Yun-Gui⁵,Huang He⁶,Wu De-Pei⁷,Li Yan⁸,Yan Xiao-Jing⁹,Yan Jin-Song¹⁰,Li Jian-Yong¹¹,Wang Shuai¹²,Huang Xiao-Jun¹³,Jia Wei²,Chen Zhu¹,Chen Sai-Juan¹

Affiliation:

1. Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China,

2. State Key Laboratory of Medical Genomics, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China,

3. Rui Jin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai,

4. Department of Hematology, Institute of Hematology, the First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, China,

5. Zhejiang Institute of Hematology, First Hospital affiliated to Zhejiang University School of Medicine, Hangzhou, China,

6. Bone Marrow Transplantation Center, The First Affiliated Hospital, College of Medical, Zhejiang University, Hangzhou, China,

7. The first Affiliated Hospital of Soochow University,

8. Hematology, First Affiliated Hospital of China Medical University, Liaoning, China, Shenyang, China,

9. State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital affiliated with Shanghai Jiao Tong, Shanghai, China,

10. Second Hospital affiliated to Dalian Medical University, Dalian, Dalian, China,

11. Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China,

12. First Hospital affiliated to Nanjing Medical University, Nanjing, China,

13. Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

Abstract

Abstract Abstract 1433 BACKGROUND High levels of 2-HG in serum were found among AML cases with IDH1/IDH2 mutations. However, the impact of 2-HG levels on biological characteristics and clinical outcomes has not been systematically evaluated in a large cohort of AML patients. METHODS Serum 2-HG levels in 699 patients with hematologic malignancies, including 405 AML patients, were measured by GC-TOFMS. Clinical prognostic power of 2-HG and genetic risk factors associated with 2-HG were also evaluated in AML patients. RESULTS Among all patients with hematopoietic malignancies investigated, high serum 2-HG levels were observed only in AML group. 64 out of 405 (15.8%) AML patients displayed aberrantly higher levels (7.14±2.11μg/ml) of 2-HG. Compared to cases with normal 2-HG (3.65±1.02μg/ml), these patients showed a higher prevalence in AML-M0/M1 subtypes, a closer correlation with mutated IDH1/2 genes, a distinct gene expression profile and an aberrant DNA methylation status in bone marrow blasts. Additionally, the patients with high 2-HG were associated with higher serum levels of α-ketoglutarate (α-KG) and glutamate, suggesting presence of impaired metabolic pathway involved in the biosynthesis of 2-HG. Univariate and multivariate analyses indicate that high level of 2-HG is among the most significant negative indicators for complete remission (CR) rate, overall survival (OS) and event-free survival (EFS) either in all AML cases or in cases with cytogenetically normal AML (CN-AML). CONCLUSIONS Serum 2-HG is an independent prognostic marker in AML. Patients with high 2-HG had significantly higher frequency of IDH1/IDH2 gene mutations and unfavorable prognosis compared to those with normal 2-HG. Disclosures: No relevant conflicts of interest to declare.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry