GSE130385
Temporal transcriptional response from primary human chronic lymphocytic leukemia (CLL)-cells after B-cell receptor stimulation.
The B-cell receptor (BCR) signaling is crucial for the pathophysiology of most leukemias and lymphomas  originated from mature B lymphocytes and has emerged as a new therapeutic target, especially for chronic lymphocytic leukemia (CLL). However, the precise mechanisms by which BCR signaling controls neoplastic B-cell proliferation are ill characterized.   This work was performed using primary leukemic cells of untreated patients at initial stage of CLL (Binet stage A / Rai 0) presenting biological characteristics of aggressive form of the disease (unmutated IGHV genes and ZAP70 protein expression). In order to mimic the primary leukemogenic step occurring in vivo, this study focused on the BCR-dependent proliferation of CLL cells induced ex vivo using anti-IgM, together with mandatory co-stimulating factors (CD40L, IL-4 and IL-21) (Schleiss, Sci Rep, 2019). Cell proliferation was objectivized by the emergence of proliferative clusters and the presence of more than 25% of CLL cells that did undergo division within the cell culture at day 6. To capture the specific actors of the proliferative response in these samples, we also included non-proliferating control CLL samples. Gene expression was analyzed by RNA-seq before stimulation (T0) and at the time points 1h, 1h30, 3h30, 6h30, 12h, 24h, 48h and 96h after cell stimulation (n=54 data points), the latest time points corresponding to the emergence of the proliferation clusters. Overall design: Temporal transcriptional response (T0 + 8 time points) of primary chronic lymphocytic leukemia (CLL) cells after BCR engagement ex vivo (anti-IgM, IL-4, CD40Ligand and IL-21) of 3 Proliferating (P1, P2, P3) and 3 Non Proliferating samples (NP1, NP2, NP3).