Multidimensional single-cell analysis of BCR signaling reveals proximal activation defect as a hallmark of chronic lymphocytic leukemia B cells.

ABSTRACT:

Purpose

Chronic Lymphocytic Leukemia (CLL) is defined by a perturbed B-cell receptor-mediated signaling machinery. We aimed to model differential signaling behavior between B cells from CLL and healthy individuals to pinpoint modes of dysregulation.

Experimental design

We developed an experimental methodology combining immunophenotyping, multiplexed phosphospecific flow cytometry, and multifactorial statistical modeling. Utilizing patterns of signaling network covariance, we modeled BCR signaling in 67 CLL patients using Partial Least Squares Regression (PLSR). Results from multidimensional modeling were validated using an independent test cohort of 38 patients.

Results

We identified a dynamic and variable imbalance between proximal (pSYK, pBTK) and distal (pPLCγ2, pB

SUBMITTER: Palomba ML 

PROVIDER: S-EPMC3906024 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature