Levels of AgR (BCR) expression are regulated during B cell development, activation, and induction of tolerance. The mechanisms responsible for and consequences of this regulation are poorly understood. We have described a class of DNA-based autoantigen-reactive B cell that down-regulates BCR expression during development to mature follicular phenotype. In this study, we show that at immature st...

The Philadelphia (Ph) chromosome, the product of t(9:22), is the cytogenetic hallmark of chronic myelogenous leukemia. The c-abl oncogene on chromosome 9 is translocated to the Ph chromosome and linked to a breakpoint cluster region (bcr), which is part of a large bcr gene. This results in the formation of a bcr-c-abl fusion gene, which is transcribed into an 8.5 kb chimeric mRNA encoding a 210...

In Chronic Myeloid Leukemia 80% of patients present alternative splice variants involving BCR exons 1, 13 or 14 and ABL exon 4, with a consequent impairment in the reading frame of the ABL gene. Therefore BCR/ABL fusion proteins (BCR/ABL-OOF) are characterized by an in-frame BCR portion followed by an amino acids sequence arising from the out of frame (OOF) reading of the ABL gene. The product ...

To define how the signaling pathways that mediate the B cell receptor (BCR) death pathway differ from those responsible for CD95/Fas-mediated death, we compared the BCR and Fas death pathways in two human B cell lines, B104 and BJAB. Both BCR- and Fas-induced apoptosis are blocked by the peptide cysteine protease inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (ZVAD (mlz)), demonstra...

The IgM FcR (FcμR) promotes B cell survival, but the molecular mechanism remains largely unknown. We show using FcμR(-/-) and wild-type mice that FcμR specifically enhanced B cell survival induced by BCR cross-linking with F(ab')2-anti-IgM Abs while having no effect on survival when the B cells were activated by CD40 ligation or LPS stimulation. FcμR expression was markedly upregulated by anti-...

We studied the clinical, hematologic, cytogenetic and molecular biologic features in four patients with Philadelphia (Ph) negative chronic myeloid leukemia (CML). In all four cases the clinical and hematologic characteristics were indistinguishable from Ph positive CML. Cytogenetic analysis showed a normal karyotype in two patients and chromosomal translocations apparently not affecting chromos...

We have previously shown that the chimeric gene ABL-BCR, formed on the derivative chromosome 9q+ as a result of the t(9;22) translocation, is transcriptionally active in 65% of chronic myeloid leukemia patients. We have now used the same technique, reverse transcription/polymerase chain reaction amplification of ABL-BCR transcripts, to study nine patients with Philadelphia (Ph) chromosome-posit...

The p210(bcr-abl) protein was shown to inhibit apoptosis induced by DNA damaging agents. Apoptotic DNA fragmentation is delayed in the bcr-abl+ K562 and KCL-22 compared with the bcr-abl- U937 and HL-60 cell lines when treated with etoposide concentrations that induce similar DNA damage in the four cell lines. By the use of a cell-free system, we show that nuclei from untreated cells that expres...

BACKGROUND AND OBJECTIVES Baseline creatinine (BCr) is frequently missing in AKI studies. Common surrogate estimates can misclassify AKI and adversely affect the study of related outcomes. This study examined whether multiple imputation improved accuracy of estimating missing BCr beyond current recommendations to apply assumed estimated GFR (eGFR) of 75 ml/min per 1.73 m(2) (eGFR 75). DESIGN,...

BCR-mediated antigen processing occurs at immunologically relevant antigen concentrations and hinges on the trafficking of antigen-BCR (Ag-BCR) complexes to class II-containing multivesicular bodies (MVBs) termed MIICs. However, the molecular mechanism underlying the trafficking of Ag-BCR complexes to and within MIICs is not well understood. In contrast, the trafficking of the epidermal growth ...