Unmet Need in Essential Thrombocythemia and Polycythemia Vera

Kishtagari, Ashwin; Gerds, Aaron T.

doi:10.1016/j.hoc.2021.01.003

Cited by 4 publications

(2 citation statements)

References 31 publications

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“…Despite the progress in the last years in the treatment of ET, none of the available therapies can change the outcome of the disease (94). Up to date, none of the therapies improve overall survival and prevent leukemic or brotic transformation (95). For these reasons, there is a need to identify a new potential molecular mechanism affecting the drug resistance to improve the ET outcome.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 and JAK2 mRNA level in essential thrombocythaemia depends on the driver mutational status and the bone marrow fibrosis grade

Lewandowski

Kanduła

Gniot

et al. 2022

Preprint

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Background: JAK-STAT pathway activation leads to an enhanced activity of the promoter of CD274 (PDL1) coding programmed death-1 receptor ligand (PD-L1), increased PD-L1 level and the immune escape of myeloproliferative neoplasms (MPN) cells. It has been postulated that the bone marrow failure, bone marrow myeloid metaplasia, and changes in the molecular characteristics of the malignant clone(s) during MPN outcome may influence the JAK2 and PDL1 gene expression. Aim: to evaluate the PDL1 mRNA and JAK2 mRNA level in molecularly defined essential thrombocythaemia (ET) patients (pts) during disease progression to post-ET- myelofibrosis (post-ET-MF). Methods: the study group consisted of 162 ET pts, including 30 diagnosed with post-ET-MF. Results: the JAK2V617F, CALR, and MPL mutations were found in 59.3%, 19.1%, and 1.2% of pts, respectively. The total JAK2 mRNA level (V617F+WT) did not differ according to the JAK2 haplotypeGGCC_46/1 or the type of driver defect. No copy-number alternations of the JAK2, PDL1, and PDCDL1G2 (PDL2) genes were found. The level of PD-L1 was significantly higher in the JAK2V617F than in the JAK2WT, CALR mutation-positive, and triple-negative pts. The PD-L1 mRNA level was weakly correlated with both the JAK2V617F variant allele frequency (VAF), and with the JAK2V617F allele mRNA level. The total JAK2 level in post-ET-MF pts was lower than in ET pts despite the lack of differences in the JAK2V617F VAF. In addition, the PD-L1 level was lower in post-ET-MF. The detailed analysis has shown that the decrease in JAK2 and PD-L1 mRNA levels depended on the bone marrow fibrosis grade. The PDL1 expression showed no difference in relation to the genotype of 46/1 haplotype, hemoglobin concentration, hematocrit value, leukocyte, and platelet counts. Conclusion: the study confirmed the correlation between the PD-L1 and JAK2 mRNA level in ET pts. The observed drop of the total JAK2 and PD-L1 levels during the ET progression to the post-ET-MF may reflect the changes in the JAK2V617F positive clone proliferative potential and the PD-L1 level related immunosuppressive effect. This decrease could explain the lack of efficacy of the pembrolizumab in patients with advanced post-ET-MF and post-polycythemia vera myelofibrosis which was recently reported.

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Section: Discussionmentioning

confidence: 99%

PD-L1 and JAK2 mRNA level in essential thrombocythaemia depends on the driver mutational status and the bone marrow fibrosis grade

Lewandowski

Kanduła

Gniot

et al. 2022

Preprint

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“…Conventional risk stratification for ET identifies high risk (age > 60 years and/or history of thrombosis) or low risk (absence of either high-risk feature) patients. Only high-risk patients undergo cytoreductive therapy [ 102 , 103 , 104 , 105 , 106 ].…”

Section: The Ev World Of Etmentioning

confidence: 99%

The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

Catani

Cavo

Palandri³

2021

Cells

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Myeloproliferative Neoplasms (MPN) are acquired clonal disorders of the hematopoietic stem cells and include Essential Thrombocythemia, Polycythemia Vera and Myelofibrosis. MPN are characterized by mutations in three driver genes (JAK2, CALR and MPL) and by a state of chronic inflammation. Notably, MPN patients experience increased risk of thrombosis, disease progression, second neoplasia and evolution to acute leukemia. Extracellular vesicles (EVs) are a heterogeneous population of microparticles with a role in cell-cell communication. The EV-mediated cross-talk occurs via the trafficking of bioactive molecules such as nucleic acids, proteins, metabolites and lipids. Growing interest is focused on EVs and their potential impact on the regulation of blood cancers. Overall, EVs have been suggested to orchestrate the complex interplay between tumor cells and the microenvironment with a pivotal role in “education” and “crafting” of the microenvironment by regulating angiogenesis, coagulation, immune escape and drug resistance of tumors. This review is focused on the role of EVs in MPN. Specifically, we will provide an overview of recent findings on the involvement of EVs in MPN pathogenesis and discuss opportunities for their potential application as diagnostic and prognostic biomarkers.

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Prognostic value of response to first-line hydroxyurea according to IPSET stratification in essential thrombocythemia

Santaliestra,

Garrote,

Noya

et al. 2024

Leukemia

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Unmet Need in Essential Thrombocythemia and Polycythemia Vera

Cited by 4 publications

References 31 publications

PD-L1 and JAK2 mRNA level in essential thrombocythaemia depends on the driver mutational status and the bone marrow fibrosis grade

PD-L1 and JAK2 mRNA level in essential thrombocythaemia depends on the driver mutational status and the bone marrow fibrosis grade

The Power of Extracellular Vesicles in Myeloproliferative Neoplasms: “Crafting” a Microenvironment That Matters

Prognostic value of response to first-line hydroxyurea according to IPSET stratification in essential thrombocythemia

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