Emerging roles of ADAM6 and PRSS1 as novel diagnostic/prognostic biomarkers for acute lymphoblastic and myeloid leukemia in adults

Abstract

Background

Acute leukemia is an aggressive, highly heterogeneous hematological malignancy. A Disintegrin And Metalloproteinase Domain-6 (ADAM6), a member of ADAMs family, has emerged recently as a potential novel player in pediatric acute lymphoblastic leukemia (ALL), and its function remains largely elusive. Serine Protease-1 (PRSS1) is another emerging molecular mediator in cancer development. However, its role in acute leukemia has not been adequately studied. Interestingly, ADAM6 and PRSS1 were identified among the genes with the highest percentage of chromosomal changes in profiled B-cell precursor ALL patients. Both are emerging novel mediators of extracellular matrix (ECM) remodeling. Thus, this study was designed to investigate the roles of ADAM6 and PRSS1 in ALL and acute myeloid leukemia (AML) in adults.

Methods

Adult patients with de novo ALL (n = 36), de novo AML (n = 40), and healthy control subjects (n = 55) were enrolled in this study. Circulating serum levels of ADAM6 and PRSS1 were measured by ELISA technique.

Results

Serum levels of ADAM6 were significantly higher in ALL and AML patients compared to healthy control subjects (208.7(178.3–337.3), 186.4(155.3–479.6), and 78.6(55.8–101.8) pg/ml, p < 0.0001), respectively. Whereas, serum levels of PRSS1 were found to be significantly lower in ALL and AML patients compared to healthy controls (175.1(153.7–232.2), 177.9(145.3–206.4), and 247.5(204.3–375.3) ng/ml, p < 0.0001), respectively. Both ADAM6 and PRSS1 exhibited a very good diagnostic potential by ROC analyses. ADAM6 levels significantly varied between CD22⁺/CD22⁻ and CD45⁺/CD45⁻, while PRSS1 levels significantly varied between HLA-DR⁺/HLA-DR⁻ ALL patients, suggesting their prognostic implications. Also, ADAM6 and PRSS1 were found to be significantly correlated with each other.

Conclusion

The results of the current study portray ADAM6 and PRSS1 as new potential diagnostic/prognostic biomarkers and potential therapeutic targets in adult acute leukemia patients, and shed light on their role as novel interrelated mediators possibly implicated in tumor micro-environment remodeling.