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 cut-off 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.
Highlights
Acute lymphoblastic leukemia (ALL) is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued
Design and Methods: Histidine-rich glycoprotein (HRG) was quantitatively measured in serum by enzyme-linked immunosorbent assay (ELISA) and its expression was assessed by real-time PCR in 35 patients with acute lymphoblastic leukemia (ALL) and compared to same 25 ALL patients after induction therapy and 30 age and sex matched healthy control subjects
The best cutoff value for HRG-serum protein levels in ALL detected by Receiver Operating Characteristic (ROC) curves, considering healthy subjects as control group, was 63.55 pg/ml with 90.0% sensitivity and 100.0% specificity, and for HRG-RNA was 0.955 with 83.3% sensitivity and 100% specificity (p < 0.01), Figure 2 and Table 2
Summary
Acute lymphoblastic leukemia (ALL) is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued. More than 80% of adult patients with Philadelphia chromosome (Ph)-negative ALL achieve complete remission (CR) with conventional induction therapy, their 5-year survival is only 30% - 40%. 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. The serum HRG level showed a significant positive correlation with its expression level, bone marrow blast percentage, peripheral blood blast count, P < 0.01. Its serum and expression levels were positively related to the poor risk Philadelphia chromosome; P < 0.01. 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
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