Diagnostic and Prognostic Significance of Histidine-Rich Glycoprotein in Acute Lymphoblastic Leukemia

Abstract

Background: Histidine-rich glycoprotein (HRG), a multifunctional plasma protein, has a regulatory role in homeostasis, angiogenesis, and immunity; which in turn could greatly affect tumor control and metastasis. Objectives: To assess the possible role of HRG in acute lymphoblastic leukemia (ALL) tumorgenesis and follow-up. Design and Methods: HRG was quantitatively measured in serum by ELISA and its expression was assessed by real-time PCR (qPCR) in 35 patients with ALL and compared to same 25 ALL patients after induction therapy and 30 age and sex matched healthy control subjects. Results: HRG-serum protein (at cutoff value 63.55 pg/ml) and HRG-RNA (at cutoff value 0.955) were positive in all ALL patients before therapy, but in only 76% after therapy for HRG-protein and 60% for HRG-RNA and they could not be detected in the control group; P < 0.001. Additionally, the serum HRG level showed a significant positive correlation with its expression level, bone marrow blast percentage, peripheral blood blast count, P < 0.01. Also its serum and expression levels were positively related to the poor risk Philadelphia chromosome; P < 0.01. Conclusions: HRG (protein and RNA) might be considered as a novel diagnostic and prognostic marker in ALL. HRG-serum protein level, detected by simple methodology of ELISA, has more significant advantages than its expression level, motivating its application in large clinical studies as a potential marker.

Decreased Levels of Histidine-Rich Glycoprotein in Advanced Lung Cancer: Association with Prothrombotic Alterations

“…HRG levels may also be increased in some malignancies as reported by Matboli et al who observed higher HRG levels in breast cancer (median, 17.1 mg/dl) compared to benign breast lesions (median, 1.56 mg/dl) and the control (median, 1.1 mg/dl) group [ 26 ]. Ahmed et al [ 28 ] have observed in acute lymphoblastic leukemia that both HRG serum levels and protein RNA expression decreased during the leukemia treatment. Taken together, the present study shows that advanced lung cancer is associated with decreased HRG levels, which appears to be a common feature in most advanced cancers.…”

“…Moreover, HRG by promoting tumor-associated macrophage polarization into an antitumor phenotype [ 24 , 25 ] may result in tumor growth inhibition and it is a possible mechanism of cancer progression. Available data on HRG in cancer patients is inconsistent [ 26 – 28 ]. To our knowledge, no reports on HRG in lung cancer and its role in prothrombotic alterations have been published until now.…”

Construction of 2DE-Patterns of Plasma Proteins: Aspect of Potential Tumor Markers

“…Many of these functions are involved in tumor progression and antitumor response [301]. For instance, its serum and expression levels were positively related to the poor risk in acute lymphoblastic leukemia (ALL) patients, and HRG might be a diagnostic biomarker, with high sensitivity and specificity [202]. But it was shown that a decreased HRG level occurs in advanced LC and is associated with the disease stage and hypofibrinolysis [203].…”