TY - JOUR
T1 - A gene expression assay based on chronic lymphocytic leukemia activation in the microenvironment to predict progression
AU - Abrisqueta, Pau
AU - Medina, Daniel
AU - Villacampa Javierre, Guillermo
AU - Lu, Junyan
AU - Alcoceba, Miguel
AU - Carabia, Júlia
AU - Boix, Joan
AU - Tazón-Vega, Barbara
AU - Iacoboni, Gloria
AU - Bobillo, Sabela
AU - Marín-Niebla, Ana
AU - González, Marcos
AU - Zenz, Thorsten
AU - Crespo, Marta
AU - Bosch José, Francesc Xavier
PY - 2022
Y1 - 2022
N2 - Several gene expression profiles with a strong correlation with patient outcomes have been previously described in chronic lymphocytic leukemia (CLL), although their applicability as biomarkers in clinical practice has been particularly limited. Here we describe the training and validation of a gene expression signature for predicting early progression in patients with CLL based on the analysis of 200 genes related to microenvironment signaling on the NanoString platform. In the training cohort (n = 154), the CLL15 assay containing a 15-gene signature was associated with the time to first treatment (TtFT) (hazard ratio [HR], 2.83; 95% CI, 2.17-3.68; P <.001). The prognostic value of the CLL15 score (HR, 1.71; 95% CI, 1.15-2.52; P =.007) was further confirmed in an external independent validation cohort (n = 112). Notably, the CLL15 score improved the prognostic capacity over IGHV mutational status and the International Prognostic Score for asymptomatic early-stage (IPS-E) CLL. In multivariate analysis, the CLL15 score (HR, 1.83; 95% CI, 1.32-2.56; P <.001) and the IPS-E CLL (HR, 2.23; 95% CI, 1.59-3.12; P <.001) were independently associated with TtFT. The newly developed and validated CLL15 assay successfully translated previous gene signatures such as the microenvironment signaling into a new gene expression-based assay with prognostic implications in CLL.
AB - Several gene expression profiles with a strong correlation with patient outcomes have been previously described in chronic lymphocytic leukemia (CLL), although their applicability as biomarkers in clinical practice has been particularly limited. Here we describe the training and validation of a gene expression signature for predicting early progression in patients with CLL based on the analysis of 200 genes related to microenvironment signaling on the NanoString platform. In the training cohort (n = 154), the CLL15 assay containing a 15-gene signature was associated with the time to first treatment (TtFT) (hazard ratio [HR], 2.83; 95% CI, 2.17-3.68; P <.001). The prognostic value of the CLL15 score (HR, 1.71; 95% CI, 1.15-2.52; P =.007) was further confirmed in an external independent validation cohort (n = 112). Notably, the CLL15 score improved the prognostic capacity over IGHV mutational status and the International Prognostic Score for asymptomatic early-stage (IPS-E) CLL. In multivariate analysis, the CLL15 score (HR, 1.83; 95% CI, 1.32-2.56; P <.001) and the IPS-E CLL (HR, 2.23; 95% CI, 1.59-3.12; P <.001) were independently associated with TtFT. The newly developed and validated CLL15 assay successfully translated previous gene signatures such as the microenvironment signaling into a new gene expression-based assay with prognostic implications in CLL.
U2 - 10.1182/bloodadvances.2022007508
DO - 10.1182/bloodadvances.2022007508
M3 - Article
C2 - 35973197
SN - 2473-9529
VL - 6
SP - 5763
EP - 5773
JO - Blood advances
JF - Blood advances
ER -