HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses
Cristina Scielzo, … , Massimo Alessio, Federico Caligaris-Cappio
Cristina Scielzo, … , Massimo Alessio, Federico Caligaris-Cappio
Published June 1, 2005
Citation Information: J Clin Invest. 2005;115(6):1644-1650. https://doi.org/10.1172/JCI24276.
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Research Article Oncology

HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses

Abstract

We used a proteomic approach for identifying molecules involved in the pathogenesis of chronic lymphocytic leukemia (CLL). We investigated 14 patients who were completely concordant for IgVH mutational status (unmutated vs. mutated), CD38 expression (positive vs. negative), and clinical behavior (progressive vs. stable); these patients were characterized as having either poor or good prognoses. The 2 patient subsets differed in the expression of hematopoietic lineage cell-specific protein 1 (HS1). In patients with poor prognoses, most HS1 protein was constitutively phosphorylated, whereas only a fraction was phosphorylated in patients with good prognoses. This difference was investigated in a larger cohort of 26 unselected patients. The survival curve of all 40 patients analyzed revealed that patients with predominately phosphorylated HS1 experience a significantly shorter median survival time. As HS1 is a protein pivotal in the signal cascade triggered by B cell receptor (BCR) stimulation, we studied its pattern of expression following BCR engagement. Normal mature B cells stimulated by anti-IgM shifted the non- or less-phosphorylated form of HS1 toward the more phosphorylated form. Naive B cells showed both HS1 forms while memory B cells expressed mainly the phosphorylated fraction. These data indicate a central role for antigen stimulation in CLL and suggest a new therapeutic target for patients with aggressive disease.

Authors

Cristina Scielzo, Paolo Ghia, Antonio Conti, Angela Bachi, Giuseppe Guida, Massimo Geuna, Massimo Alessio, Federico Caligaris-Cappio

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Figure 1

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2-DE proteomic analysis of purified CLL cells. (A) The square identifies...
2-DE proteomic analysis of purified CLL cells. (A) The square identifies 2 close protein spots with the same Mr of 79 kDa and different pIs, 4.83 and 4.86, which were identified as HS1 proteins by MALDI-TOF MS analysis (see Results). IEF, isoelectric focusing. (B) Both right and left protein spots were expressed in 2D gels obtained from 2 representative CLL patients with good prognoses (subset 1) while only the more acidic one was present in 2D gels obtained from 2 representative CLL patients with poor prognoses (subset 2). Arrows indicate the left and right protein spots identified as HS1. (C) Proteins obtained from 5 representative CLL patients were resolved on 2-DE that was either silver stained (left panel) or transferred onto nitrocellulose and incubated with an anti-HS1 antibody (right panel). One representative case is shown. The antibody hybridizes in an area corresponding to the protein spots of interest. WB, Western blot.