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基质细胞衍生因子-1 基因多态性与急性髓系白血病患者发病风险增加相关。

Association of SDF-1 Gene Polymorphism with Increased Risk of Acute Myeloid Leukemia Patients.

机构信息

Hematology Unit, Department of Clinical Pathology, Mansoura Faculty of Medicine, Mansoura University, Egypt.

Clinical Hematology Unit, Department of Internal Medicine, Oncology Center, Mansoura University, Mansoura, Egypt.

出版信息

Asian Pac J Cancer Prev. 2021 Apr 1;22(4):1035-1043. doi: 10.31557/APJCP.2021.22.4.1035.

DOI:10.31557/APJCP.2021.22.4.1035
PMID:33906294
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8325146/
Abstract

BACKGROUND

Acute myeloid leukemia (AML) is a heterogenous group of disorders that emerge from the malignant transformation of hematopoietic stem cells. Chemokine stromal cell-derived factor 1(SDF-1) and its receptor CXC receptor 4 (CXCR4) has an essential role in dissemination of blast cells. Study aimed to detect CXCR4 expression and the SDF-1 (rs1801157) gene polymorphisms and correlate them with prognosis and outcome in AML patients.

SUBJECTS AND METHODS

The study was conducted on 60 de-novo AML patients, and 60 healthy controls. SDF-1 (rs1801157) gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and CXCR4 expression was done using flow cytometry analysis.

RESULTS

SDF-1 dominant model (AG+AA) had higher risk AML (p 0.002). CXCR4positive cases were associated significantly with toxic manifestations (p 0.019), lower CR rates (p 0.004), and unfavorable cytogenetics (p 0.027). Multivariate analysis showed that combined CXCR4positive with dominant SDF-1 considered as independent prognostic factor for shorter overall survival (OS) in AML patients (p 0.031).

CONCLUSION

SDF-1 dominant model had a higher risk to develop AML, and CXCR4 positive expression predicts poor prognosis in AML patients and it could represent a targeted therapy in AML. In addition, CXCR4 could be easily integrated into the initial routine diagnostic work up of AML.
.

摘要

背景

急性髓系白血病（AML）是一组异质性疾病，源于造血干细胞的恶性转化。趋化因子基质细胞衍生因子 1（SDF-1）及其受体 CXC 受体 4（CXCR4）在白血病细胞播散中起重要作用。本研究旨在检测 AML 患者中 CXCR4 表达和 SDF-1（rs1801157）基因多态性，并将其与预后和结果相关联。

受试者和方法

该研究纳入了 60 例初发 AML 患者和 60 例健康对照者。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测 SDF-1（rs1801157）基因多态性，通过流式细胞术分析检测 CXCR4 表达。

结果

SDF-1 优势模型（AG+AA）发生 AML 的风险更高（p 0.002）。CXCR4 阳性病例与毒性表现显著相关（p 0.019），缓解率较低（p 0.004），细胞遗传学不良（p 0.027）。多变量分析表明，联合 CXCR4 阳性与优势 SDF-1 模型被认为是 AML 患者总生存期（OS）较短的独立预后因素（p 0.031）。

结论

SDF-1 优势模型发生 AML 的风险更高，而 CXCR4 阳性表达预示 AML 患者预后不良，可能成为 AML 的靶向治疗靶点。此外，CXCR4 可容易地整合到 AML 的初始常规诊断工作中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/7f25b7d9e135/APJCP-22-1035-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/16d10fa3c293/APJCP-22-1035-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/0185e637badf/APJCP-22-1035-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/77a68f1b994a/APJCP-22-1035-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/60718ca78dd4/APJCP-22-1035-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/816fc26edc04/APJCP-22-1035-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/7f25b7d9e135/APJCP-22-1035-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/16d10fa3c293/APJCP-22-1035-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/0185e637badf/APJCP-22-1035-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/77a68f1b994a/APJCP-22-1035-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/60718ca78dd4/APJCP-22-1035-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72ae/8325146/7f25b7d9e135/APJCP-22-1035-g006.jpg

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