The BAF chromatin remodeling complex is a novel target of spliceosome dysregulation in SF3B1-mutated chronic lymphocytic leukemia

Type: Transcriptome Analysis
Archiver: European Genome-Phenome Archive (EGA)

3 Datasets 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001009729	RNA-sequencing data for 100 stereotypes CLL subset cases. Illumina based short-read sequencing data from a 100 samples from patients with CLL. Oxford Nanopore Technologies long-read sequencing data from 5 samples from patients with CLL.	Illumina HiSeq 2500 MinION	100
EGAD50000000754	The NFKBIE gene, which encodes the NF-κB inhibitor IκBε, is mutated in 3-7% of patients with chronic lymphocytic leukemia (CLL). The most recurrent alteration is a 4-bp frameshift deletion associated with NF-κB activation in leukemic B cells and poor clinical outcome. To study the functional consequences of NFKBIE gene inactivation, both in vitro and in vivo, we engineered CLL B cells and CLL-prone mice to stably down-regulate NFKBIE expression and investigated its role in controlling NF-κB activity and disease expansion. We found that IκBε loss leads to NF-κB pathway activation and promotes both migration and proliferation of CLL cells in a dose-dependent manner. Importantly, NFKBIE inactivation was sufficient to induce a more rapid expansion of the CLL clone in lymphoid organs and contributed to the development of an aggressive disease with a shortened survival in both xenografts and genetically modified mice. IκBε deficiency was associated with an alteration of the MAPK pathway, also confirmed by RNA-sequencing in NFKBIE-mutated patient samples, and resistance to the BTK inhibitor ibrutinib. In summary, our work underscores the multimodal relevance of the NF-κB pathway in CLL and paves the way to translate these findings into novel therapeutic options.	Illumina HiSeq 2500	8
EGAD50000000755	Oxford Nanopore Technologies based long-read RNA sequencing data from 5 patients with stereotyped subset CLL. The BAM files were aligned against hg19 reference genome.	MinION	5

Publications	Citations
IκBε deficiency accelerates disease development in chronic lymphocytic leukemia. Bordini J, Lenzi C, Frenquelli M, Morabito A, Pseftogas A, Belloni D, Mansouri L, Tsiolas G, Perotta E, Ranghetti P, Gandini F, Genova F, Hägerstrand D, Gavriilidis G, Keisaris S, Pechlivanis N, Davi F, Kay NE, Langerak AW, Pospisilova S, Scarfò L, Makris A, Psomopoulos FE, Stamatopoulos K, Rosenquist R, Campanella A, Ghia P. Leukemia 38: 2024 1287-1298	0
The non-canonical BAF chromatin remodeling complex is a novel target of spliceosome dysregulation in SF3B1-mutated chronic lymphocytic leukemia. Hägerstrand D, Oder B, Cortese D, Qu Y, Binzer-Panchal A, Österholm C, Del Peso Santos T, Rabbani L, Asl HF, Skaftason A, Ljungström V, Lundholm A, Koutroumani M, Haider Z, Jylhä C, Mollstedt J, Mansouri L, Plevova K, Agathangelidis A, Scarfò L, Armand M, Muggen AF, Kay NE, Shanafelt T, Rossi D, Orre LM, Pospisilova S, Barylyuk K, Davi F, Vesterlund M, Langerak AW, Lehtiö J, Ghia P, Stamatopoulos K, Sutton LA, Rosenquist R. Leukemia 38: 2024 2429-2442	0

Publications

Citations

IκBε deficiency accelerates disease development in chronic lymphocytic leukemia.
Bordini J, Lenzi C, Frenquelli M, Morabito A, Pseftogas A, Belloni D, Mansouri L, Tsiolas G, Perotta E, Ranghetti P, Gandini F, Genova F, Hägerstrand D, Gavriilidis G, Keisaris S, Pechlivanis N, Davi F, Kay NE, Langerak AW, Pospisilova S, Scarfò L, Makris A, Psomopoulos FE, Stamatopoulos K, Rosenquist R, Campanella A, Ghia P. Leukemia 38: 2024 1287-1298

The non-canonical BAF chromatin remodeling complex is a novel target of spliceosome dysregulation in SF3B1-mutated chronic lymphocytic leukemia.
Hägerstrand D, Oder B, Cortese D, Qu Y, Binzer-Panchal A, Österholm C, Del Peso Santos T, Rabbani L, Asl HF, Skaftason A, Ljungström V, Lundholm A, Koutroumani M, Haider Z, Jylhä C, Mollstedt J, Mansouri L, Plevova K, Agathangelidis A, Scarfò L, Armand M, Muggen AF, Kay NE, Shanafelt T, Rossi D, Orre LM, Pospisilova S, Barylyuk K, Davi F, Vesterlund M, Langerak AW, Lehtiö J, Ghia P, Stamatopoulos K, Sutton LA, Rosenquist R. Leukemia 38: 2024 2429-2442