Hairy Cell Leukemia Cell Line JOK1 +/- RhoH Reconstitution
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ABSTRACT:
PROVIDER: PRJNA658103 | ENA |
REPOSITORIES: ENA
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Project description:The hairy cell leukemia line JOK1 with low RhoH expression was stably trasfected with either an empty expression vector or this same vector expressing human RhoH. The transcriptomes of these two daughter lines were then compared by differential microarray analysis The hairy cell leukemia line JOK1 with low RhoH expression was stably trasfected with either an empty expression vector or this same vector expressing human RhoH. The transcriptomes of these two daughter lines were then compared by differential microarray analysis
2021-01-03 | GSE156483 | GEO
Project description:The Adult T-Cell Leukemia/Lymphoma Cell Line KK1 +/- RhoH Reconstitution
| PRJNA947956 | ENA
Project description:The adult T-cell leukemia/lymphoma cell line KK1 with low RhoH expression was stably transfected with either an empty expression vector or this same vector expressing human RhoH. The transcriptomes of these two daughter lines were then compared by differential microarray analysis
2023-03-23 | GSE228059 | GEO
Project description:Molecular signatures for Hairy cell leukemia
| PRJNA676121 | ENA
Project description:Analysis of the expression profile of 298 mRNA's, measured with the nCounter (Nanostring Technologies platform), in 13 samples from the peripheral blood of Hairy cell leukemia patients Hairy cell leukemia (HCL) is a rare chronic B-cell malignancy, characterized by infiltration of bone marrow, blood and spleen by typical “hairy cells” that bear the BRAFV600E mutation. However, in addition to the intrinsic activation of the MAP kinase pathway as a consequence of the BRAFV600E mutation, the potential participation of other signaling pathways to the pathophysiology of the disease remains unclear. Using mRNA gene expression profiling based on the Nanostring technology and the analysis of 290 genes with crucial roles in B-cell lymphomas, we defined a 17 gene expression signature specific for HCL. Our analysis revealed intrinsic activation of the non-canonical NF-B pathway with underexpression of BIRC2 and BIRC3, two specific non-canonical NF-B inhibitors. Western blots confirmed activation of this pathway with increased processing of p100 in primary HCL samples. Separate analysis of samples from classical and variant forms of hairy cell leukemia showed almost similar mRNA expression profiles apart from overexpression in vHCL of the immune checkpoints CD274 and PDCD1LG2 and underexpression of FAS. Our results provide a better understanding of the pathogenesis of HCL and describe new and potential targets for treatment approaches and guidance for studies in the molecular mechanisms of HCL.
2020-11-12 | GSE161279 | GEO
Project description:<p>To understand the genetic mechanisms driving variant and IGHV4-34 expressing hairy-cell leukemia, we performed whole exome sequencing of tumor/normal pairs from ten patients.</p>
| phs000671.v1.p1 | EGA
Project description:<p>To understand the genetic mechanisms driving variant and IGHV4-34 expressing hairy-cell leukemia, we performed whole exome sequencing of tumor/normal pairs from ten patients.</p>
| phs000671 | dbGaP
Project description:Hairy cell leukemia (HCL) shows unique clinico-pathological and biological features. HCL responds well to purine analogues but relapses are frequent and novel therapies are required. BRAF-V600E is the key driver mutation in HCL and distinguishes it from other B-cell lymphomas, including HCL-like leukemias/lymphomas (HCL-variant and splenic marginal zone lymphoma). The kinase-activating BRAF-V600E mutation also represents an ideal therapeutic target in HCL. Here, we investigated the biological and therapeutic importance of the activated BRAF-MEK-ERK pathway in HCL by exposing in vitro primary leukemic cells purified from 26 patients to clinically available BRAF (Vemurafenib; Dabrafenib) or MEK (Trametinib) inhibitors. Results were validated in vivo in samples from Vemurafenib-treated HCL patients within a phase-2 clinical trial. BRAF and MEK inhibitors caused, specifically in HCL (but not HCL-like) cells, marked MEK/ERK dephosphorylation, silencing of the BRAF-MEK-ERK pathway transcriptional output, loss of the HCL-specific gene expression signature, downregulation of the HCL markers CD25, TRAP and cyclin-D1, smoothening of leukemic cells' hairy surface, and, eventually, apoptosis. Apoptosis was partially blunted by co-culture with bone marrow stromal cells antagonizing MEK-ERK dephosphorylation. This protective effect could be counteracted by combined BRAF and MEK inhibition. Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL.
2014-12-12 | GSE63790 | GEO
Project description:Hairy cell leukemia (HCL) shows unique clinico-pathological and biological features. HCL responds well to purine analogues but relapses are frequent and novel therapies are required. BRAF-V600E is the key driver mutation in HCL and distinguishes it from other B-cell lymphomas, including HCL-like leukemias/lymphomas (HCL-variant and splenic marginal zone lymphoma). The kinase-activating BRAF-V600E mutation also represents an ideal therapeutic target in HCL. Here, we investigated the biological and therapeutic importance of the activated BRAF-MEK-ERK pathway in HCL by exposing in vitro primary leukemic cells purified from 26 patients to clinically available BRAF (Vemurafenib; Dabrafenib) or MEK (Trametinib) inhibitors. Results were validated in vivo in samples from Vemurafenib-treated HCL patients within a phase-2 clinical trial. BRAF and MEK inhibitors caused, specifically in HCL (but not HCL-like) cells, marked MEK/ERK dephosphorylation, silencing of the BRAF-MEK-ERK pathway transcriptional output, loss of the HCL-specific gene expression signature, downregulation of the HCL markers CD25, TRAP and cyclin-D1, smoothening of leukemic cells' hairy surface, and, eventually, apoptosis. Apoptosis was partially blunted by co-culture with bone marrow stromal cells antagonizing MEK-ERK dephosphorylation. This protective effect could be counteracted by combined BRAF and MEK inhibition. Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL. Analysis of differential gene expression in primary leukemic cells purified from peripheral blood of 6 HCL patients (from A to F), treated with Vemurafenib 1000 nM, in comparison with vehicle-treated (DMSO) HCL cells, for 48 hours or/and 72 hours. 24 gene expression profiles were analysed.
2014-12-12 | E-GEOD-63790 | biostudies-arrayexpress
Project description:Activation-Induced Cytidine Deaminase (AID) is required for somatic hypermutation and immunoglobulin (Ig) class switch recombination in germinal center B lymphocytes. Occasionally, AID targets non-Ig genes, thereby contributing to B cell lymphomagenesis. We recently reported aberrant expression of AID in BCR-ABL1-driven acute lymphoblastic leukemia (ALL). To elucidate the biological significance of aberrant AID expression, we studied loss of AID function in a murine model of BCR-ABL1 ALL. Mice transplanted with BCR-ABL1-transduced AID-/- bone marrow had prolonged survival as compared to mice transplanted with leukemia cells generated from AID+/+ bone marrow. Consistent with a causative role of AID in genetic instability, AID-/- leukemia had a decreased frequency of amplifications, deletions and a lower frequency of mutations in non-Ig genes including Pax5 and Rhoh as compared to AID+/+ leukemias. AID-/- and AID+/+ ALL cells showed a markedly distinct gene expression pattern as determined by principle component analysis, with 2,365 genes differentially expressed. In contrast to AID+/+ leukemia, AID-/- ALL cells failed to downregulate a number of tumor suppressor genes such as Rhoh, Cdkn1a (p21), and Blnk (SLP65). We conclude that AID accelerates clonal evolution in BCR-ABL1 ALL by enhancing genetic instability, aberrant somatic hypermutation, and by transcriptional inactivation of tumor suppressor genes. Experiment Overall Design: We used microarrays to detect differences in gene expression profiles between AID expressing leukemia and AID deficient leukemia
2009-07-05 | E-GEOD-16751 | biostudies-arrayexpress