Clinical and molecular profile of a Brazilian cohort of patients with classical BCR-ABL1-negative myeloproliferative neoplasms

Porto-Soares, Moysés Antonio; Oliveira, Rafael Daltro De; Cortopassi, Gabriel Macedo; Machado-Neto, João Agostinho; Palma, Leonardo Carvalho; Figueiredo-Pontes, Lorena Lôbo de

doi:10.1016/j.htct.2019.07.008

Cited by 6 publications

(9 citation statements)

References 19 publications

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“…We also noticed that JAK2V617F patients had a lower platelet count compared to CALR mutated patients without statistically significant. Our results were supported by previous reports and other studies 33–35 …”

Section: Discussionsupporting

confidence: 94%

“…Our results were supported by previous reports and other studies. [33][34][35] Tefferi et al have also shown that patients with CALR mutations were younger and had higher platelet count and lower hemoglobin and leucocytes counts compared with JAK2V617F patients. 32 Several studies have shown that JAK2V617F may increase the likelihood of thrombotic events in ET patients.…”

Section: Sexmentioning

confidence: 99%

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Hematological relevance of JAK2 V617F and calreticulin mutations in Tunisian patients with essential thrombocythemia

Abdelghani

Hammami

Zidi

et al. 2022

Clinical Laboratory Analysis

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Background:The genetic investigation of essential thrombocythemia(ET) has highlighted the presence of driver mutations in ET. Janus kinase JAK2V617F and calreticulin(CALR) mutations are the most frequent driver mutations and have significantly improved the molecular diagnosis of ET. The impact of genetic heterogeneity on clinical features has not been fully elucidated. This is the first study which aimed to determine the frequency of JAK2V617F and CALR exon9 mutations in Tunisian ET patients and to establish the correlation between hematological characteristics and mutational status.Methods: This study included Tunisian patients suspected with ET and was conducted between September 2017 and March 2021. Genomic DNA of patients was isolated from peripheral blood samples. JAK2V617F was detected by AS-PCR and CALR mutations were detected by PCR/direct sequencing. Clinical and hematological characteristics were also analyzed.Results: Two hundred and fifty ET patients were enrolled in this study. JAK2V617F mutation was found in 166/250 (66.4%) of patients, whereas CALR mutations were detected in 27/84 (32.1%) patients without JAK2V617F. Compared with JAK2V617Fpositive patients, those with CALR mutations showed lower hemoglobin level and lower leucocytes count (p = 0.007 and p = 0.004,respectively). CALR type 2 was the most frequent mutation of CALR detected in 55.55% of CALR mutated. Six of seven patients with thrombotic events harbored JAK2V617F mutation. Conclusion:The prevalence of driver mutations JAK2V617F or CALR mutations was 77.2% in Tunisian ET patients. Moreover, patients with JAK2 V617F mutation had a higher risk of thrombosis. The mutational status is necessary to improve the diagnosis and contribute to the therapeutic decisions.

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Section: Discussionsupporting

confidence: 94%

Section: Sexmentioning

confidence: 99%

Hematological relevance of JAK2 V617F and calreticulin mutations in Tunisian patients with essential thrombocythemia

Abdelghani

Hammami

Zidi

et al. 2022

Clinical Laboratory Analysis

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“…These somatic mutations lead to abnormal activation of the JAK pathway, resulting in constitutive activation of their downstream effectors, specially STATs ( 2 , 3 ). JAK2V617F is the most frequent driver mutation in MPN patients: it is detected in more than 90% of PV patients, and in about 50–60% of ET and PMF patients ( 4 , 5 ). The CALR mutation is found in about 20–30% of ET and PMF patients, and is the second most frequent MPN-mutation ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…JAK2V617F is the most frequent driver mutation in MPN patients: it is detected in more than 90% of PV patients, and in about 50–60% of ET and PMF patients ( 4 , 5 ). The CALR mutation is found in about 20–30% of ET and PMF patients, and is the second most frequent MPN-mutation ( 4 , 5 ). Triple negative and MPL mutation are present in less than 12% of ET and PMF patients ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Soluble Mediator Signatures of Patients With Philadelphia Chromosome-Negative Myeloproliferative Neoplasms

et al. 2021

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BackgroundEssential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are clonal hematological diseases classified as Philadelphia chromosome-negative myeloproliferative neoplasms (MPN). MPN pathogenesis is associated with the presence of somatic driver mutations, bone marrow (BM) niche alterations, and tumor inflammatory status. The relevance of soluble mediators in the pathogenesis of MPN led us to analyze the levels of cytokines, chemokines, and growth factors related to inflammation, angiogenesis and hematopoiesis regulation in the BM niche of MPN patients.MethodsSoluble mediator levels in BM plasma samples from 17 healthy subjects, 28 ET, 19 PV, and 16 PMF patients were determined using a multiplex assay. Soluble mediator signatures were created from categorical analyses of high mediator producers. Soluble mediator connections and the correlation between plasma levels and clinic-laboratory parameters were also analyzed.ResultsThe soluble mediator signatures of the BM niche of PV patients revealed a highly inflammatory and pro-angiogenic milieu, with increased levels of chemokines (CCL2, CCL5, CXCL8, CXCL12, CXCL10), and growth factors (GM-CSF M-CSF, HGF, IFN-γ, IL-1β, IL-6Ra, IL-12, IL-17, IL-18, TNF-α, VEGF, and VEGF-R2). ET and PMF patients presented intermediate inflammatory and pro-angiogenic profiles. Deregulation of soluble mediators was associated with some clinic-laboratory parameters of MPN patients, including vascular events, treatment status, risk stratification of disease, hemoglobin concentration, hematocrit, and red blood cell count.ConclusionsEach MPN subtype exhibits a distinct soluble mediator signature. Deregulated production of BM soluble mediators may contribute to MPN pathogenesis and BM niche modification, provides pro-tumor stimuli, and is a potential target for future therapies.

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“…XPO1 (encoding exportin protein) involvement (Case 16) was demonstrated in primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) [ 26 ]. On the contrary, the mutation of the JAK2 gene best known as a driver in myeloproliferative neoplasias [ 27 ] presented with the alteration c.1177C > G; p.Leu393Val (Case 15) and was rather considered non-pathogenic SNP according to NCBI dsSNP search results.…”

Section: Discussionmentioning

confidence: 99%

Cell-Free Total Nucleic Acid-Based Genotyping of Aggressive Lymphoma: Comprehensive Analysis of Gene Fusions and Nucleotide Variants by Next-Generation Sequencing

Mokánszki

Bicskó

Gergely

et al. 2021

Cancers

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Chromosomal translocations and pathogenic nucleotide variants both gained special clinical importance in lymphoma diagnostics. Non-invasive genotyping from peripheral blood (PB) circulating free nucleic acid has been effectively used to demonstrate cancer-related nucleotide variants, while gene fusions were not covered in the past. Our prospective study aimed to isolate and quantify PB cell-free total nucleic acid (cfTNA) from patients diagnosed with aggressive lymphoma and to compare with tumor-derived RNA (tdRNA) from the tissue sample of the same patients for both gene fusion and nucleotide variant testing. Matched samples from 24 patients were analyzed by next-generation sequencing following anchored multiplexed polymerase chain reaction (AMP) for 125 gene regions. Eight different gene fusions, including the classical BCL2, BCL6, and MYC genes, were detected in the corresponding tissue biopsy and cfTNA specimens with generally good agreement. Synchronous BCL2 and MYC translocations in double-hit high-grade B-cell lymphomas were obvious from cfTNA. Besides, mutations of 29 commonly affected genes, such as BCL2, MYD88, NOTCH2, EZH2, and CD79B, could be identified in matched cfTNA, and previously described pathogenic variants were detected in 16/24 cases (66.7%). In 3/24 cases (12.5%), only the PB sample was informative. Our prospective study demonstrates a non-invasive approach to identify frequent gene fusions and variants in aggressive lymphomas. cfTNA was found to be a high-value representative reflecting the complexity of the lymphoma aberration landscape.

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Clinical and molecular profile of a Brazilian cohort of patients with classical BCR-ABL1-negative myeloproliferative neoplasms

Cited by 6 publications

References 19 publications

Hematological relevance of JAK2 V617F and calreticulin mutations in Tunisian patients with essential thrombocythemia

Hematological relevance of JAK2 V617F and calreticulin mutations in Tunisian patients with essential thrombocythemia

Bone Marrow Soluble Mediator Signatures of Patients With Philadelphia Chromosome-Negative Myeloproliferative Neoplasms

Cell-Free Total Nucleic Acid-Based Genotyping of Aggressive Lymphoma: Comprehensive Analysis of Gene Fusions and Nucleotide Variants by Next-Generation Sequencing

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