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). CXCR4 positive 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.
Highlights
Acute myeloid leukemia (AML) is a heterogenous group of disorders, in which the blast cells either not, minimally, or abnormally differentiated (Tuzuner and Bennett, 2018)
Subjects A study was conducted on 60 patients with de novo acute myeloid leukemia patients were diagnosed at the Oncology Center Mansoura University (OCMU)
Negative and Positive flow cytometric analysis of CXC receptor 4 (CXCR4) expression on AML myeloblast cells are shown in Figures 1 and 2
Summary
Acute myeloid leukemia (AML) is a heterogenous group of disorders, in which the blast cells either not, minimally, or abnormally differentiated (Tuzuner and Bennett, 2018). CXCR4 has an important role as it is the receptor for stromal derived factor (SDF-1), known as CXC ligand 12 which is a member of chemokine family and a major molecule governing hematopoietic stem cells (HSCs) maintenance, regulating the process of embryogenesis, neutrophil homeostasis, inflammatory response, tumorigenesis and infiltration (Peled et al, 2018; Pillozzi et al, 2019). Study aimed to detect CXCR4 expression and the SDF-1 (rs1801157) gene polymorphisms and correlate them with prognosis and outcome in AML patients. 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. CXCR4 could be integrated into the initial routine diagnostic work up of AML
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