The JAK2V617F mutation is associated with anomalies in the frequency of monocytes, B cells, CD8+ T cells and NK cells

Costa-Brito, Ana Raquel; Cardoso, Elsa M.; Martinez, Jorge; Arosa, Fernando A.

doi:10.1016/j.bcmd.2015.06.005

Cited by 3 publications

(3 citation statements)

References 9 publications

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“…Mounting evidence points towards a severe immune dysregulation in patients with MPN (8,9), with both early-and advanced-stage patients exhibiting increased levels of several inflammatory cytokines (10)(11)(12) and a dysregulation in the frequency of circulating immune cells (13)(14)(15)(16). Data on interferon-alpha (IFNa) efficacy in MPN patients further supports the theory of immune suppression: IFNa is an immunostimulatory drug capable of inducing long-lasting hematological and molecular remission in these patients (17,18).…”

Section: Introductionmentioning

confidence: 98%

Patients With Myeloproliferative Neoplasms Harbor High Frequencies of CD8 T Cell-Platelet Aggregates Associated With T Cell Suppression

et al. 2022

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Myeloproliferative neoplasms (MPN) are chronic cancers of the hematopoietic stem cells in the bone marrow, and patients often harbor elevated numbers of circulating platelets (PLT). We investigated the frequencies of circulating PLT-lymphocyte aggregates in MPN patients and the effect of PLT-binding on CD8 T cell function. The phenotype of these aggregates was evaluated in 50 MPN patients and 24 controls, using flow cytometry. In vitro studies compared the proliferation, cytokine release, and cytoxicity of PLT-bound and PLT-free CD8 T cells. Frequencies of PLT-CD8 T cell aggregates, were significantly elevated in MPN patients. Advanced disease stage and CALR mutation associated with the highest aggregate frequencies with a predominance of PLT-binding to antigen-experienced CD8 T cells. PLT-bound CD8 T cells showed reduction in proliferation and cytotoxic capacity. Our data suggest that CD8 T cell responses are jeopardized in MPN patients. JAK2 and CALR exon 9 mutations – the two predominant driver mutations in MPN – are targets for natural T cell responses in MPN patients. Moreover, MPN patients have more infections compared to background. Thus, PLT binding to antigen experienced CD8 T cells could play a role in the inadequacy of the immune system to control MPN disease progression and prevent recurrent infections.

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Section: Introductionmentioning

confidence: 98%

Patients With Myeloproliferative Neoplasms Harbor High Frequencies of CD8 T Cell-Platelet Aggregates Associated With T Cell Suppression

et al. 2022

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“…Immune complications are relatively common in JAK 2V617F positive MPNs, and the changing frequency and function of immune cells are the main causes of these alterations, 21 which can be a function of JAK2 V617F mutation, abnormal expression of some biological agents such as cytokines, as well as therapeutic protocols like IFN-α therapy. 20 , 87 , 97 An abnormal immunophenotype of immune-related CD markers may be a prognostic factor for predicting the immune complications. Therefore, CD markers’ evaluation based on flow cytometry can help determine the patient’s immunologic status and control these complications by appropriate therapeutic interventions.…”

Section: Discussionmentioning

confidence: 99%

“… 22 , 86 This mutation can affect the frequency and function of B, T, NK cells, and monocytes in PV patients. 87 Previous studies have shown that different lymphoid subtypes, including TCD4 + and TCD8 + cells, are significantly reduced in PMF patients compared with healthy subjects. In contrast, a small number of these patients showed an increase in BCD5 + and TCD8 + cytotoxic lymphocytes.…”

Section: Abnormal Expression Of Immune Cell Related CD Markers and Immentioning

confidence: 94%

Expression of CD markers in JAK2V617F positive myeloproliferative neoplasms: Prognostic significance

et al. 2018

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Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by the presence of JAK2V617F mutation. Thrombohemorrhagic as well as autoimmune or inflammatory phenomena are common clinical outcomes of these disorders. Recent studies have shown that abnormality in frequency and function of blood cells manifested by an alteration in CD markers’ expression patterns play a key role in these complications. So, there may be a relationship between CD markers’ expressions and prognosis of JAK2V617F positive MPNs. Therefore, in this review, we have focused on these abnormalities from the perspective of changing expressions of CD markers and assessment of the relationship between these changes with prognosis of JAK2V617F positive MPNs. It can be stated that the abnormal expression of a large number of CD markers can be used as a prognostic biomarker for clinical outcomes including thrombohememorrhagic events, as well as autoimmune and leukemic transformation in JAK2V617F positive MPNs. Considering the possible role of CD markers’ expressions in JAK2V617F MPNs prognosis, further studies are needed to confirm the relationship between the expression of CD markers with prognosis to be able to find an appropriate therapeutic approach via targeting CD markers.

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Distinctive CD8+ T cell and MHC class I signatures in polycythemia vera patients

et al. 2018

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Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by overproduction of red blood cells. We have performed a comprehensive characterization of blood immune cells for expression of naïve and memory receptors as well as βm-associated and βm-free MHC class I heavy chains, also known as closed and open conformers, respectively, in PV patients and age-matched controls (CTR). We show that the peripheral CD3CD8 T cell pool in PV patients is clearly divided into two discrete populations, a more granular CD3CD8 T cell population enriched in effector-memory CD45RA T cells (CD8 TEMRA) when compared to CTR (P < 0.001), and a less granular CD3CD8 T cell population that is completely absent in the CTR group (78 vs. 0%, P < 0.001) and is a mixture of naïve (CD8 T) and CD8 TEMRA cells expressing intermediate levels of CD28, i.e., CD3CD8CD28. While the percentage of CD3CD8 TN cells correlated positively with the number of erythrocytes, the percentage of CD3CD8 TEMRA correlated negatively with the number of platelets. Finally, we report that PV patients' lymphocytes and monocytes display lower levels of closed (W6/32) MHC-I conformers at the cell surface while exhibiting increased amounts of open (HC-10) MHC-I conformers. The implications of this distinctive immune signature are discussed.

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The JAK2V617F mutation is associated with anomalies in the frequency of monocytes, B cells, CD8+ T cells and NK cells

Cited by 3 publications

References 9 publications

Patients With Myeloproliferative Neoplasms Harbor High Frequencies of CD8 T Cell-Platelet Aggregates Associated With T Cell Suppression

Patients With Myeloproliferative Neoplasms Harbor High Frequencies of CD8 T Cell-Platelet Aggregates Associated With T Cell Suppression

Expression of CD markers in JAK2V617F positive myeloproliferative neoplasms: Prognostic significance

Distinctive CD8+ T cell and MHC class I signatures in polycythemia vera patients

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