Characterization of purine‐rich element binding protein B as a novel biomarker in acute myelogenous leukemia prognostication. Issue 2 (18th October 2017)

• Record Type: Journal Article
• Authors: Kelm, Robert J.; Lamba, Gurpreet S.; Levis, Jamie E.; Holmes, Chris E.
• Is Part Of: Journal of cellular biochemistry. Volume 119:Issue 2(2018)
• Page Start: 2073
• Page End: 2083
• Publication Date: 2017-10-18
• Subjects: AML -- CD33 -- FLT3 -- myeloid cell -- Purα -- Purβ -- ssDNA‐binding protein; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26369
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract : Acute myelogenous leukemia (AML) is an aggressive hematologic cancer characterized by infiltration of proliferative, clonal, abnormally differentiated cells of myeloid lineage in the bone marrow and blood. Malignant cells in AML often exhibit chromosomal and other genetic or epigenetic abnormalities that are useful in prognostic risk assessment. In this study, the relative expression and novel single‐stranded DNA (ssDNA) binding function of purine‐rich element binding proteins A and B (Purα and Purβ) were systematically evaluated in established leukemia cell lines and in lineage committed myeloid cells isolated from patients diagnosed with a hematologic malignancy. Western blotting revealed that Purα and Purβ are markedly elevated in CD33 + /CD66b + cells from AML patients compared to healthy subjects and to patients with other types of myeloid cell disorders. Results of in silico database analysis of PURA and PURB mRNA expression during hematopoiesis in conjunction with the quantitative immunoassay of the ssDNA‐binding activities of Purα and Purβ in transformed leukocyte cell lines pointed to Purβ as the more distinguishing biomarker of myeloid cell differentiation status. Purβ ssDNA‐binding activity was significantly increased in myeloid cells from AML patients but not from individuals with other myeloid‐related diseases. The highest levels of Purβ activity were detected in myeloid cells from primary AML patients and from AML patients displaying other risk factors forecasting a poor prognosis. Collectively, these findings suggest that the enhanced ssDNA‐binding activity of Purβ in transformed myeloid cells may serve as a unique and measurable phenotypic trait for improving prognostic risk stratification in AML. Abstract : Purine‐rich element binding protein B (PURB) is a sequence‐specific, single‐stranded DNA‐binding factor implicated in the regulation of blood cell differentiation. Expression of the PURB gene is most prominent in hematopoietic stem/progenitor cells and in transformed myeloid cells. Enhanced single‐stranded DNA‐binding activity of the PURB protein is a phenotypic feature of CD33 positive leukocytes isolated from specific subsets of patients diagnosed with acute myelogenous leukemia.