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Triple negative, JAK2V617F and CALR mutated essential thrombocythaemia patients share a unique gene expression signature [RNA-seq]

ABSTRACT: There is a unique signature pattern that is consistent across the essential thrombocythaemia (ET) population regardless of mutation status. ET phenotype may therefore, at least in part and regardless of mutation type, be driven by transcriptional mis-regulation and may propagate downstream via the MAPK, TNF and NFκB pathways with resultant JAK/STAT activation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156336 | GEO | 2021/03/02

REPOSITORIES: GEO

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Triple negative, JAK2V617F and CALR mutated essential thrombocythaemia patients share a unique gene expression signature [array]

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Patients with triple-negative, JAK2V617F- and CALR-mutated essential thrombocythemia share a unique gene expression signature.

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Triple negative, JAK2V617F and CALR mutated essential thrombocythaemia patients share a unique gene expression signature

Project description:Triple negative, JAK2V617F and CALR mutated essential thrombocythaemia patients share a unique gene expression signature

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Triple negative, JAK2V617F and CALR mutated essential thrombocythaemia patients share a unique gene expression signature [array]

Project description:Triple negative, JAK2V617F and CALR mutated essential thrombocythaemia patients share a unique gene expression signature [array]

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Triple negative, JAK2V617F and CALR mutated essential thrombocythaemia patients share a unique gene expression signature

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-03-02 | GSE156547 | GEO

Increased B cell activation is present in JAK2V617F-mutated, CALR-mutated and triple-negative essential thrombocythemia.

Project description:Essential thrombocythemia (ET) is a BCL-ABL1-negative myeloproliferative neoplasm. We have reported that increased activated B cells can facilitate platelet production mediated by cytokines regardless JAK2 mutational status in ET. Recently, calreticulin (CALR) mutations were discovered in ~30% JAK2/MPL-unmutated ET and primary myelofibrosis. Here we sought to screen for CALR mutations and to evaluate B cell immune profiles in a cohort of adult Taiwanese ET patients. B cell populations, granulocytes/monocytes membrane-bound B cell-activating factor (mBAFF) levels, B cells toll-like receptor 4 (TLR4) expression and intracellular levels of interleukin (IL)-1β/IL-6 and the expression of CD69, CD80, and CD86 were quantified by flow cytometry. Serum BAFF concentration was measured by ELISA. 48 healthy adults were used for comparison. 19 (35.2%) of 54 ET patients harbored 8 types of CALR exon 9 mutations including 4 (7.4%) patients with concomitant JAK2V617F mutations. Compared to JAK2V617F mutation, CALR mutations correlated with younger age at diagnosis (p=0.04), higher platelet count (p=0.004), lower hemoglobin level (p=0.013) and lower leukocyte count (p=0.013). Multivariate analysis adjusted for age, sex, follow-up period and hematological parameters confirmed that increased activated B cells were universally present in JAK2-mutated, CALR-mutated and triple-negative ET patients when compared to healthy adults. JAK2- and CALR-mutated ET have significantly higher fraction of B cells with TLR4 expression when compared to triple-negative ET (p=0.019 and 0.02, respectively). CALR-mutated ET had significantly higher number of CD69-positive activated B cells when compared to triple-negative ET (p=0.035). In conclusion, increased B cell activation is present in ET patients across different mutational subgroups.

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JAK2V617F mutation in CD34+ stem cells of essential thrombocythemia

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JAK2V617F mutation in CD34+ stem cells of essential thrombocythemia

Project description:The JAK2V617F mutation has been reported in about 40-60% of Essential Thrombocythemia (ET) patients. However, little is known about specific molecular abnormalities of the hematopoietic stem cell compartment of ET according to JAK2 mutation. Therefore, we compared the gene expression profiles of bone marrow (BM) CD34+ cells from 16 patients with and without the JAK2V617F mutation to identify differentially expressed genes. Keywords: cell type comparison Sample name and JAK2V617F mutation: - BM CD34+ cells from healthy subject (CTR) - ET JAK2V617F-positive: ET 1, ET 4, ET 6, ET 7, ET 8, ET 10, ET 12, ET 15 - ET JAK2V617F-negative: ET 2, ET 3, ET 5, ET 9, ET 11, ET 13, ET 14, ET 16

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