BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells

Guarini, Anna; Chiaretti, Sabina; Tavolaro, Simona; Maggio, Roberta; Peragine, Nadia; Citarella, Franca; Ricciardi, Maria Rosaria; Santangelo, Simona; Marinelli, M; Propris, Maria Stefania De; Messina, Monica; Mauro, Francesca Romana; Giudice, Ilaria Del; Foà, Robert

doi:10.1182/blood-2007-12-127688

Cited by 121 publications

(132 citation statements)

References 56 publications

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“…The notion that ZAP-70 ϩ29 and unmutated CLL cells 20,56 are more responsive to BCR stimulation and other microenvironmental signals 28 suggests that patients with high-risk disease features may be particularly well suited for alternative treatments that target the microenvironment. Indeed, early clinical data from ongoing trials with the Btk inhibitor PCI-32765 57 and the PI3K inhibitor CAL-101 58 suggest that high-risk CLL patients respond well to these agents that disrupt CLL-microenvironment interactions.…”

Section: Bcr and Bcr-associated Kinases (Syk Btk And Pi3k Delta)mentioning

confidence: 99%

Nurture versus Nature: The Microenvironment in Chronic Lymphocytic Leukemia

2011

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Section: Bcr and Bcr-associated Kinases (Syk Btk And Pi3k Delta)mentioning

confidence: 99%

Nurture versus Nature: The Microenvironment in Chronic Lymphocytic Leukemia

2011

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“…We also observed significantly higher levels of IgM expression in NOTCH1 mutated cases. It is known that IgM expression is higher in cells with increased ability to respond to external stimuli, 12,13 indicating that the NOTCH1 mutated clone might survive and expand also thanks to these interactions. Intriguingly, approximately 30% of the upregulated transcripts were located on chromosome 12.…”

Section: Gene Expression Profiling Of +12 Cll With Notch1 Mutationsmentioning

confidence: 99%

NOTCH1 mutations in +12 chronic lymphocytic leukemia (CLL) confer an unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of +12 CLL

Giudice¹,

Rossi²,

Chiaretti³

et al. 2011

Haematologica

173

128

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“…It is worthy of note that micro-array analysis revealed an increased expression of CD69 gene in UM CLL upon BCR cross-linking. 38 In fact, IgM stimulation of BCR up-regulates several genes associated with the cell cycle allowing cell growth and expansion, thus ultimately contributing to the unfavorable clinical course of these CLL patients. In addition, CD69, tested on CLL cells by flow cytometry, was found to be up-regulated on cells in the tissue microenvironment, both in bone marrow (BM) and lymph nodes (LN).…”

Section: Cd69-cd69+mentioning

confidence: 99%

CD69 is independently prognostic in chronic lymphocytic leukemia: a comprehensive clinical and biological profiling study

Poeta

Principe²,

Zucchetto³

et al. 2011

Haematologica

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BackgroundCD69 is expressed in several hemopoietic cells and is an early activation marker in chronic lymphocytic leukemia. Chronic lymphocytic leukemia is a clinically heterogeneous disease which needs novel prognostic parameters which can be easily and efficiently managed. Design and MethodsWe investigated CD69 by flow cytometry in a series of 417 patients affected by chronic lymphocytic leukemia and compared this to other biological and clinical prognosticators. ResultsCD69 was associated with Rai stages (P=0.00002), b2-microglobulin (P=0.0005) and soluble CD23 (P<0.0001). CD69 and ZAP-70 (P=0.018) or CD38 (P=0.00015) or immunoglobulin variable heavy chain gene mutations (P=0.0005) were also significantly correlated. Clinically, CD69 positive chronic lymphocytic leukemias received chemotherapy more frequently (74%; P<0.0001), and presented a shorter duration of response after fludarabine plus rituximab (P=0.010) as well as shorter progression free survival and overall survival (P<0.0001). CD69 demonstrated true additive prognostic properties, since the CD69 + plus ZAP-70 + or CD38 + or immunoglobulin variable heavy chain gene unmutated patients had the worst progression free survival and overall survival (P<0.0001). Interestingly, low CD69 expression was necessary to correctly prognosticate the longer progression free survival of patients with a low tumor burden of b2-microglobulin (P=0.002), of soluble CD23 (P=0.020), or of Rai stages 0-I (P=0.005). CD69 was confirmed to be an independent prognostic factor in multivariate analysis of progression free survival (P=0.017) and overall survival (P=0.039). ConclusionsOur data indicate that CD69 is significantly correlated with poor clinical and biological prognostic factors and is confirmed to be an independent disease prognosticator. This supports its introduction in a routine laboratory assessment and, possibly, in a prognostic scoring system for chronic lymphocytic leukemia, after an adequate standardization process.

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BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgVH unmutated chronic lymphocytic leukemia (CLL) cells

Cited by 121 publications

References 56 publications

Nurture versus Nature: The Microenvironment in Chronic Lymphocytic Leukemia

Nurture versus Nature: The Microenvironment in Chronic Lymphocytic Leukemia

NOTCH1 mutations in +12 chronic lymphocytic leukemia (CLL) confer an unfavorable prognosis, induce a distinctive transcriptional profiling and refine the intermediate prognosis of +12 CLL

CD69 is independently prognostic in chronic lymphocytic leukemia: a comprehensive clinical and biological profiling study

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