Promoter Polymorphisms in the β-2 Adrenergic Receptor Are Associated With Drug-Induced Gene Expression Changes and Response in Acute Lymphoblastic Leukemia

Pottier, Nicolas; Paugh, Steven W.; Ding, Cong; D, Pei; Yang, Wenjian; Das, Santasabuj; Eh, Cook; Ch, Pui; Mv, Relling; Cheok, Meyling; We, Evans

doi:10.1038/clpt.2010.212

Cited by 7 publications

(2 citation statements)

References 41 publications

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“…To further strengthen the existence of a unique transcriptional signature that differentiates V H 11 and non-V H 11 CLL B cells, we selected 24 robustly differentially expressed genes for validation. Some of these genes have already been shown to play a role in hematologic malignancies, including CLL ( Pim-2, Met, Rgs16, Ccdc88a, Zcchc18, Clip3 ) ( 38 – 42 ), diffuse large B cell lymphoma, follicular lymphoma ( Vav3 ) ( 43 ), acute lymphoblastic leukemia (ALL) ( Itm2a, Chst1 ) ( 44 , 45 ) or acute myeloid leukemia (AML) ( Chd3 ) ( 46 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of Distinct Unmutated Chronic Lymphocytic Leukemia Subsets in Mice Based on Their T Cell Dependency

et al. 2018

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Chronic lymphocytic leukemia (CLL) can be divided into prognostically distinct subsets with stereotyped or non-stereotyped, mutated or unmutated B cell receptors (BCRs). Individual subsets vary in antigen specificity and origin, but the impact of antigenic pressure on the CLL BCR repertoire remains unknown. Here, we employed IgH.TEμ mice that spontaneously develop CLL, expressing mostly unmutated BCRs of which ~35% harbor VH11-2/Vκ14-126 and recognize phosphatidylcholine. Proportions of VH11/Vκ14-expressing CLL were increased in the absence of functional germinal centers in IgH.TEμ mice deficient for CD40L or activation-induced cytidine deaminase. Conversely, in vivo T cell-dependent immunization decreased the proportions of VH11/Vκ14-expressing CLL. Furthermore, CLL onset was accelerated by enhanced BCR signaling in Siglec-G−/− mice or in mice expressing constitutively active Bruton's tyrosine kinase. Transcriptional profiling revealed that VH11 and non-VH11 CLL differed in the upregulation of specific pathways implicated in cell signaling and metabolism. Interestingly, principal component analyses using the 148 differentially expressed genes revealed that VH11 and non-VH11 CLL clustered with BCR-stimulated and anti-CD40-stimulated B cells, respectively. We identified an expression signature consisting of 13 genes that were differentially expressed in a larger panel of T cell-dependent non-VH11 CLL compared with T cell-independent VH11/Vκ14 or mutated IgH.TEμ CLL. Parallel differences in the expression of these 13 signature genes were observed between heterogeneous and stereotypic human unmutated CLL. Our findings provide evidence for two distinct unmutated CLL subsets with a specific transcriptional signature: one is T cell-independent and B-1 cell-derived while the other arises upon antigen stimulation in the context of T-cell help.

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Section: Resultsmentioning

confidence: 99%

Identification of Distinct Unmutated Chronic Lymphocytic Leukemia Subsets in Mice Based on Their T Cell Dependency

et al. 2018

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“…For example, ABCA1 is an auspicious therapy target in prostate cancer ( Figure S4C ) ( 44 ). A previous study has shown that high expression of ADRB2 is significantly linked to early treatment failure in ALL ( 45 ) ( Figure S4D ). In the survival analyses of these specially expressed ligand–receptor pairs, patients with higher expression of LIN7C or NRTN are prone to poor prognosis ( Figures 3D, E ).…”

Section: Resultsmentioning

confidence: 75%

Single-Cell Transcriptome Analysis Identifies Ligand–Receptor Pairs Associated With BCP-ALL Prognosis

Jiang

et al. 2021

Front. Oncol.

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B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a blood cancer that originates from the abnormal proliferation of B-lymphoid progenitors. Cell population components and cell–cell interaction in the bone marrow microenvironment are significant factors for progression, relapse, and therapy resistance of BCP-ALL. In this study, we identified specifically expressed genes in B cells and myeloid cells by analyzing single-cell RNA sequencing data for seven BCP-ALL samples and four healthy samples obtained from a public database. Integrating 1356 bulk RNA sequencing samples from a public database and our previous study, we found a total of 57 significant ligand–receptor pairs (24 upregulated and 33 downregulated) in the autocrine crosstalk network of B cells. Via assessment of the communication between B cells and myeloid cells, another 29 ligand–receptor pairs were discovered, some of which notably affected survival outcomes. A score-based model was constructed with least absolute shrinkage and selection operator (LASSO) using these ligand–receptor pairs. Patients with higher scores had poorer prognoses. This model can be applied to create predictions for both pediatric and adult BCP-ALL patients.

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β-Adrenoceptors in Cancer: Old Players and New Perspectives

Amato,

Lucchesi,

Marracci

et al. 2023

Handbook of Experimental Pharmacology

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Promoter Polymorphisms in the β-2 Adrenergic Receptor Are Associated With Drug-Induced Gene Expression Changes and Response in Acute Lymphoblastic Leukemia

Cited by 7 publications

References 41 publications

Identification of Distinct Unmutated Chronic Lymphocytic Leukemia Subsets in Mice Based on Their T Cell Dependency

Identification of Distinct Unmutated Chronic Lymphocytic Leukemia Subsets in Mice Based on Their T Cell Dependency

Single-Cell Transcriptome Analysis Identifies Ligand–Receptor Pairs Associated With BCP-ALL Prognosis

β-Adrenoceptors in Cancer: Old Players and New Perspectives

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