B‐cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms: Influence of ruxolitinib, interferon‐α2, or combination treatment

Sørensen, Anders Lindholm; Bjørn, Mads Emil; Riley, Caroline Hasselbalch; Holmström, Morten Orebo; Andersen, Mads Hald; Svane, Inge Marie; Mikkelsen, Stine Ulrik; Skov, Vibe; Kjær, Lasse; Hasselbalch, Hans Carl; Nielsen, Claus Henrik

doi:10.1111/ejh.13292

Cited by 8 publications

(5 citation statements)

References 34 publications

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“…The adverse reactions of patients treated with IFN are mainly flu-like symptoms, which are relieved after discontinuation of treatment or application of symptomatic drug treatment that is tolerated by most patients. For PV patients, the use of IFN therapy can effectively avoid phlebotomy [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Clinical Significance and Safety of Interferon in the Treatment of Chronic Myeloproliferative Tumors

Yin

et al. 2022

Journal of Oncology

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Objective. To investigate the clinical significance and safety of interferon in the treatment of chronic myeloproliferative tumors (MPN). Methods. In this prospective study, a total of 120 patients with advanced chronic MPN admitted to our hospital between April 2016 and August 2020 were assessed for eligibility and recruited, including 62 patients with JAK2V617F mutation-positive ET (ET group) and 58 patients with JAK2V617F mutation-positive PV (PV group). 62 patients with JAK2V617F mutation-positive ET were assigned (1 : 1) to receive interferon-α (IFN-α) or hydroxyurea (HU). A similar subgrouping method for treatment of IFN-α and HU was introduced to patients with JAK2V617F mutation-positive PV. Outcome measures included efficacy and adverse reactions. Results. For patients with JAK2V617F mutation-positive ET and PV, there were no significant differences in the overall response rate between the groups treated with IFN-α or HU ( P > 0.05 ); however, the patients treated with IFN-α had a significantly higher 5-year progression-free survival (PFS) than those treated with HU ( P < 0.05 ). IFN-α was associated with a significantly lower incidence of disease progression, thrombotic events, splenomegaly, myelofibrosis, nausea, and vomiting and a higher incidence of hematological adverse reactions and flu-like symptoms versus HU ( P < 0.05 ). After six months of treatment, the PV group had 12 cases of hematological response both in the IFN-α subgroup and the HU subgroup and fewer PV patients treated with IFN-α required phlebotomy versus those treated with HU ( P < 0.05 ), in which 4 patients in the IFN-α subgroup had no hematological response and 6 patients in the HU subgroup had no hematological response. There was no significant difference in the number of cases with phlebotomy between the two subgroups of PV patients without hematological response ( P > 0.05 ). Conclusion. The use of IFN in the treatment of JAK2V617F mutation-positive ET and PV patients yields a prominent clinical effect by prolonging PFS and avoiding phlebotomy for JAK2V617F mutation-positive PV patients.

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Section: Discussionmentioning

confidence: 99%

Analysis of the Clinical Significance and Safety of Interferon in the Treatment of Chronic Myeloproliferative Tumors

Yin

et al. 2022

Journal of Oncology

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“…Opposing effects were observed for B cells, where Ruxolitinib treatment normalized the decreased numbers of B cells in MPN patients to physiological levels. The underlying mechanism remains enigmatic [ 187 ].…”

Section: The Effects Of Jakinibs On the Immune System: Focus On Cytotoxic Lymphocytesmentioning

confidence: 99%

Untwining Anti-Tumor and Immunosuppressive Effects of JAK Inhibitors—A Strategy for Hematological Malignancies?

Klein

Stoiber

Sexl

et al. 2021

Cancers

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The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway propagates signals from a variety of cytokines, contributing to cellular responses in health and disease. Gain of function mutations in JAKs or STATs are associated with malignancies, with JAK2V617F being the main driver mutation in myeloproliferative neoplasms (MPN). Therefore, inhibition of this pathway is an attractive therapeutic strategy for different types of cancer. Numerous JAK inhibitors (JAKinibs) have entered clinical trials, including the JAK1/2 inhibitor Ruxolitinib approved for the treatment of MPN. Importantly, loss of function mutations in JAK-STAT members are a cause of immune suppression or deficiencies. MPN patients undergoing Ruxolitinib treatment are more susceptible to infections and secondary malignancies. This highlights the suppressive effects of JAKinibs on immune responses, which renders them successful in the treatment of autoimmune diseases but potentially detrimental for cancer patients. Here, we review the current knowledge on the effects of JAKinibs on immune cells in the context of hematological malignancies. Furthermore, we discuss the potential use of JAKinibs for the treatment of diseases in which lymphocytes are the source of malignancies. In summary, this review underlines the necessity of a robust immune profiling to provide the best benefit for JAKinib-treated patients.

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“…Nevertheless, when mutational status is taken into account, no link has been identified between JAK2, calreticulin (CALR), or MPL mutational burden and PD-1/PD-L1 expression in cells. However, Sorensen et al demonstrated that treatment with the JAK2 inhibitor ruxolitinib, alone or combined with interferon-alpha (IFNa), lowered the high expression levels of PD-1 and PD-L1 in samples from MF and PV patients compared with healthy donors [ 127 ].…”

Section: Targeting the Pd-1/pd-l1 Axis In Mpnmentioning

confidence: 99%

Heat Shock Proteins and PD-1/PD-L1 as Potential Therapeutic Targets in Myeloproliferative Neoplasms

Almeida

Regimbeau

Jego

et al. 2020

Cancers

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Myeloproliferative neoplasms (MPN) are a group of clonal disorders that affect hematopoietic stem/progenitor cells. These disorders are often caused by oncogenic driver mutations associated with persistent Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling. While JAK inhibitors, such as ruxolitinib, reduce MPN-related symptoms in myelofibrosis, they do not influence the underlying cause of the disease and are not curative. Due to these limitations, there is a need for alternative therapeutic strategies and targets. Heat shock proteins (HSPs) are cytoprotective stress-response chaperones involved in protein homeostasis and in many critical pathways, including inflammation. Over the last decade, several research teams have unraveled the mechanistic connection between STAT signaling and several HSPs, showing that HSPs are potential therapeutic targets for MPN. These HSPs include HSP70, HSP90 (chaperoning JAK2) and both HSP110 and HSP27, which are key factors modulating STAT3 phosphorylation status. Like the HSPs, the PD-1/PD-L1 signaling pathway has been widely studied in cancer, but the importance of PD-L1-mediated immune escape in MPN was only recently reported. In this review, we summarize the role of HSPs and PD-1/PD-L1 signaling, the modalities of their experimental blockade, and the effect in MPN. Finally, we discuss the potential of these emerging targeted approaches in MPN therapy.

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B‐cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms: Influence of ruxolitinib, interferon‐α2, or combination treatment

Cited by 8 publications

References 34 publications

Analysis of the Clinical Significance and Safety of Interferon in the Treatment of Chronic Myeloproliferative Tumors

Analysis of the Clinical Significance and Safety of Interferon in the Treatment of Chronic Myeloproliferative Tumors

Untwining Anti-Tumor and Immunosuppressive Effects of JAK Inhibitors—A Strategy for Hematological Malignancies?

Heat Shock Proteins and PD-1/PD-L1 as Potential Therapeutic Targets in Myeloproliferative Neoplasms

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