Disease relevance of TDGF2

• In CR2, LFS was not influenced by the length of CR1 (53% +/- 11% in CR1 < 9.5 months compared with 50% +/- 12% in later relapses) [1].
• Treatment-related mortality rates were equivalent (p=0.51) between CR1 and CR2, as well as between Philadelphia chromosome (Ph) positive (Ph(+))and Ph(-) (p=0.23) ALL patients [2].
• Immunobiology of CR2, the B lymphocyte receptor for Epstein-Barr virus and the C3d complement fragment [3].
• The adenoviral E1A CR2 mutant dl922-947 has potent activity in ovarian cancer [4].
• This in turn resulted in an efficient binding of opsonized HIV to CR2-expressing B cells, thus facilitating B cell-mediated transmission of HIV to T cells [5].

High impact information on TDGF2

• CR2 ligands include complement C3d and Epstein-Barr virus glycoprotein 350/220 [6].
• Complement receptor 2 (CR2/CD21) is an important receptor that amplifies B lymphocyte activation by bridging the innate and adaptive immune systems [6].
• One determinant of this narrow tropism is human CR2, the only viral receptor within the superfamily of proteins that contain short consensus repeats (SCRs) [7].
• Here, Constantine Tsoukas and John Lambris review the studies of CR2 expression in T cells and offer some speculation on its possible biological significance [8].
• With both systems CR2 expression was limited to B cells, and was undetectable on T cells, monocytes, or neutrophils [9].

Chemical compound and disease context of TDGF2

• Immunoprecipitation studies with either anti-CR2 or anti-C3 have identified CR2, the R for C3d,g and EBV, as a major covalent and noncovalent binding site for C3 deposition on Raji cells during alternative pathway activation [10].
• High dose melphalan (HDM 110-140 mg/m2) and total body irradiation (TBI, 10.5 Gy, single fraction) followed by infusion of autologous bone marrow (ABMT) was evaluated for toxicity and efficacy in 24 children with acute lymphoblastic leukaemia (ALL) in second (CR2) or third remission (CR3) [11].

Biological context of TDGF2

• This region of Tax corresponds to a consensus amphipathic helix, and single point mutations targeted to amino acids on the face of this helix abolish interaction with CR2 and dramatically reduce Tax transcription function [12].
• We also characterize the region of Tax responsible for interaction with CR2 and show that the previously identified transactivation domain of Tax (amino acids 312 to 319) participates in CR2 binding [12].
• CR2 is a complement activator and the covalent binding site for C3 during alternative pathway activation by Raji cells [10].
• Here we present a model for this CR2-dependent complement activation [13].
• This analysis revealed sequences with regulatory effects on CR2 gene expression, however, these transcriptional controlling sequences did not act in a tissue specific fashion [14].

Anatomical context of TDGF2

• These molecules were found to be independent, non-linked, B cell surface structures, because capping CR1, CR2, sIgM, or sIgD with a specific antibody did not affect the distribution of the remainder of these molecules [15].
• The distribution for autologous bone marrow transplantation (ABMT) was 671 in first complete remission (CR1) and 196 in CR2 [16].
• CR1 and CR2, however, could not be shown on either mononuclear or multinuclear osteoclasts [17].
• C3 deposition in human fetal tibia primary spongiosa was localised immunohistochemically and complement receptors CR1, CR2, CR3, and CR4 were localised cellularly [17].
• In the present study, we investigated the presence of EBV receptor (CR2 or CD21) on neutrophils by cytofluorometry using five different anti-CD21 monoclonal antibodies (MoAbs), as well as fluoroscein isothiocyanate-EBV (FITC-EBV) [18].

Associations of TDGF2 with chemical compounds

• Pretransplantation regimes were: total-body irradiation (TBI), 456; busulfan plus cyclophosphamide (BU-CY) 174; marrow purging with mafosfamide, 269 (corresponding to 26% of all patients in CR1 and 41% in CR2) [16].
• The type 2 complement receptor, CR2, a B lymphocyte surface glycoprotein, is known to be a component of the EBV receptor [19].
• Dibutyryl cAMP increased the DNA-binding activity of a nuclear protein that recognized specifically a CR2 promoter-defined oligonucleotide in human B cell lines [20].
• Covalently bound C3b was dissociated from CR2 by hydroxylamine, indicating attachment via an ester bond [10].
• Genomic DNA starting immediately 5' of the sequence encoding the CR2 signal peptide was subcloned upstream of the bacterial chloramphenicol acetyltransferase gene for analysis of functional promoter and enhancer sites [14].

Other interactions of TDGF2

• The 2-year leukemia-free survival (LFS) was 42% +/- 5% (59% +/- 11% in CR1, 50% +/- 8% in CR2, and 21% +/- 9% for children not in CR) [1].
• The actuarial probability of relapse is 20%, 26%, and 48% for those transplanted in CR1, CR2, and CR3, respectively [21].
• The 3 year probability of disease-free survival (DFS) was influenced by disease stage at ABMT: CR1 48%, CR2 28%, CR3 plus CR4 15% [22].

Analytical, diagnostic and therapeutic context of TDGF2

• Sixty-four patients underwent transplantation in first remission (CR1), 16 in CR2 or CR3, and 47 patients had relapsed ALL or primary induction failure (PIF) [23].
• The 5-year event-free survival (EFS) rates for patients transplanted in CR1, CR2, and CR3 are 42%, 43%, and 25%, respectively, at median follow-up times of 57, 54, and 72 months, respectively [21].
• With the restriction of a shorter follow-up, the results achieved with the BU-CY combinations (LFS and relapse rate at 3 years, CR1 47 +/- 6 and 45 +/- 7%; CR2, 37 +/- 9 and 50 +/- 10%) did not differ from those with TBI or other chemotherapy combinations [16].
• Relapse was the most common cause of treatment failure in patients transplanted in CR2 [2].
• In our single center study, we performed RT-PCR monitoring in 14 patients with t(8;21) in CR1 (n = 13) and/or CR2 (n = 4) [24].

References