IgD cross-linking induces gene expression profiling changes and enhances apoptosis in chronic lymphocytic leukemia cells

2013 ◽  
Vol 37 (4) ◽  
pp. 455-462 ◽  
Author(s):  
Simona Tavolaro ◽  
Nadia Peragine ◽  
Sabina Chiaretti ◽  
Maria Rosaria Ricciardi ◽  
Sara Raponi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells ◽  
Cross Linking

scholarly journals Gene Expression Profiling Predicts Sensitivity of Chronic Lymphocytic Leukemia Cells to Dasatinib

HemaSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. e514
Author(s):  
Tamara J. Blätte ◽  
Marcin M. Machnicki ◽  
Eliza Glodkowska-Mrowka ◽  
Anna Dolnik ◽  
Marta Karp ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Lymphocytic Leukemia ◽  
Leukemia Cells

B-Cell Scaffold Protein with Ankyrin Repeats (BANK1) Is Differentially Expressed in ZAP-70 Negative Compared to ZAP-70 Positive Chronic Lymphocytic Leukemia Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2938-2938
Author(s):  
Frank Dicker ◽  
Susanne Schnittger ◽  
Claudia Schoch ◽  
Alexander Kohlmann ◽  
Wei-Min Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Differentially Expressed Genes ◽  
Expression Profiling ◽  
Lymphocytic Leukemia ◽  
Differentially Expressed ◽  
Cell Scaffold

Abstract The lack of somatic mutations of the immunoglobulin variable heavy chain (IgVH) gene has been established as poor prognostic marker for chronic lymphocytic leukemia (CLL) patients at early stage disease. Expression of the non receptor tyrosine kinase zeta chain associated protein (ZAP-70) was proposed as a surrogate marker for an unmutated IgVH, however, up to 30% discordant samples have been reported depending on the respective study. B cell receptor (BCR) mediated signaling is enhanced by ZAP-70 expression in CLL cells in vitro and ZAP-70 expression also tends to decrease the time from diagnosis to treatment irrespective of the IgVH status. Therefore, we wanted to identify differentially expressed genes between the ZAP-70 positive and negative CLLs by gene expression profiling of peripheral blood mononuclear cells (PBMCs) using Affymetrix microarrays (HG-U133 Plus 2.0). ZAP-70 expression was analyzed by quantitative real time PCR of CD19 purified (purity > 99%) PBMCs (n=62) using a LightCycler instrument. Expression of ZAP-70 mRNA was normalized against the housekeeping gene ABL and a relative quantitation against Jurkat T cells as a calibrator was performed. Results are expressed as normalized ratio and a cut-off of 0.5 normalized ratio gave the best correlation to the IgVH status with 77% concordant samples between ZAP-70 expression and the IgVH status. The discordant samples consisted of 5 unmutated IgVHs in the ZAP-70 negative group and 9 mutated in the ZAP-70 positive group. In a second step PBMCs of the same samples were analyzed by gene expression profiling and differentially expressed genes were identified by t-test. Among the two best genes that could be used in a classification algorithm (SVM) to distinguish between the 2 subsets with 92% accuracy were ZAP-70 and B cell scaffold protein with ankyrin repeats (BANK1). The expression of BANK1 was increased 3–4-fold in the ZAP-70 negative compared to the ZAP-70 positive CLL subset (P = 0,001). In the literature, BANK1 has been identified in human BCR expressing B cells and seems to be B cell restricted. In B cells the scaffolding protein BANK1 enhances BCR-mediated Ca2+-signaling, a signaling pathway that is also enhanced by ZAP-70 expression in CLL B cells. Based on these data we show that increased BANK1 expression correlates with a ZAP-70 negative status in CLL B cells. The functional consequences of BANK1 expression in the ZAP-70 negative subset of CLL B cells, which are usually associated with a more favorable prognosis, still need to be established further.

The Role Of PRDM1 and Its Interacting Proteins In The Pathogenesis Of Chronic Lymphocytic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2865-2865
Author(s):  
Ashima Shukla ◽  
Nagendra K Chaturvedi ◽  
Shantaram S Joshi ◽  
Philip Bierman ◽  
Adam Cornish ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Poor Prognosis ◽  
Cellular Proliferation ◽  
Good Prognosis ◽  
Lymphocytic Leukemia ◽  
Negative Regulator ◽  
Time To Treatment

Abstract Chronic Lymphocytic Leukemia (CLL) represents the most common adult leukemia in western countries, affecting approximately 10,000 individuals every year in United States of America. In order to develop effective therapeutic strategies there is a need to understand the precise molecular events associated with CLL development and progression. In an attempt to understand the process we performed transcriptome analysis of CLL cells from peripheral blood (PB) of 7 good prognosis and 8 poor prognosis patients. Additionally to validate the results further, we have utilized gene expression profiling data of CLL cells from 77 good or poor prognosis patients. Using transcriptome and gene expression profiling, we identified PR Domain Zinc Finger Protein1 (PRDM1) as one of the candidate tumor suppressor genes in CLL. PRDM1/BLIMP1 is a transcriptional repressor which is crucial for terminal differentiation of mature B cells into plasma cells. PRDM1 has been shown to promote differentiation by repressing genes essential for B cell receptor signaling and cellular proliferation. Our results demonstrated that PRDM1 expression was significantly (p < 0.05) decreased in CLL cells from poor prognosis compared to good prognosis CLL cases (Figure 1). In addition, to determine the clinical significance, the expression levels of PRDM1 were found to correlate with time to treatment in CLL patients (Figure 2). Lower expression of PRDM1 was associated (p=0.001) with shorter time to treatment in CLL (n = 40). Furthermore, using IPA analyses we identified PRDM1 interacting partners. Among those, there was increased expression of BCL2, PAX5, EHMT2, SPIB and decreased expression of BCL6, IRF4, BCR, CASP3, pFOS, TP53 and HDAC2 in CLL cells from poor prognosis patients in comparison with good prognosis. Also we have observed the differential expression of TLE1, a co-repressor molecule associated with PRDM1 and member of the Groucho family of proteins.Figure1Transcript levels of PRDM1 in Good Prognosis and Poor Prognosis.Figure1. Transcript levels of PRDM1 in Good Prognosis and Poor Prognosis.Figure2Clinical correlation of PRDM1 expression with time to treatment.Figure2. Clinical correlation of PRDM1 expression with time to treatment. Together these results are suggestive of a role for PRDM1 as a negative regulator of CLL aggressiveness and progression. These studies warranted additional investigation to elucidate the mechanism of PRDM1 mediated CLL progression and to identify a therapeutic target. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Integrative prognostic models predict long-term survival after immunochemotherapy in chronic lymphocytic leukemia patients

Haematologica ◽  
2021 ◽  
Author(s):  
Johannes Bloehdorn ◽  
Julia Krzykalla ◽  
Karlheinz Holzmann ◽  
Andreas Gerhardinger ◽  
Billy Michael Chelliah Jebaraj ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Lymphocytic Leukemia ◽  
Gene Expression Profiling ◽  
Heavy Chain ◽  
Expression Profiling ◽  
Progression Free Survival ◽  
Immunoglobulin Heavy Chain ◽  
Lymphocytic Leukemia ◽  
Prognostic Models ◽  
Variable Gene

Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab can induce longterm remissions in patients with chronic lymphocytic leukemia. Treatment efficacy with Bruton's tyrosine kinase inhibitors was found similar to fludarabine, cyclophosphamide and rituximab in untreated chronic lymphocytic leukemia patients with a mutated immunoglobulin heavy chain variable gene. To identify patients who specifically benefit from fludarabine, cyclophosphamide and rituximab, we developed integrative models including established prognostic parameters and gene expression profiling. Gene expression profiling was conducted on n=337 CLL8 trial samples, “core” probe sets were summarized on gene levels and RMA normalized. Prognostic models were built using penalized Cox proportional hazards models with the smoothly clipped absolute deviation penalty. We identified a prognostic signature of less than a dozen genes, which substituted for established prognostic factors, including TP53 and immunoglobulin heavy chain variable gene mutation status. Independent prognostic impact was confirmed for treatment, β2-microglobulin and del(17p) regarding overall survival and for treatment, del(11q), del(17p) and SF3B1 mutation for progression-free survival. The combination of independent prognostic and gene expression profiling variables performed equal to models including only established non-gene expression profiling variables. Gene expression profiling variables showed higher prognostic accuracy for patients with long progression-free survival compared to categorical variables like the immunoglobulin heavy chain variable gene mutation status and reliably predicted overall survival in CLL8 and an independent cohort. Gene expression profiling based prognostic models can help to identify patients who specifically benefit from fludarabine, cyclophosphamide and rituximab treatment. The CLL8 trial is registered under EUDRACT- 2004-004938-14 and ClinicalTrials.gov Identifier NCT00281918.

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