Ruxolitinib treatment improves muscle mass in patients with myelofibrosis

Lucijanić, Marko; Galušić, Davor; Sorić, Ena; Sedinić, Martina; Čubela, Marta; Korunić, Renata Huzjan; Pejša, Vlatko; Kušec, Rajko

doi:10.1007/s00277-020-04243-8

Cited by 11 publications

(6 citation statements)

References 3 publications

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“…Myelofibrosis is defined a myeloproliferative neoplasm that is often correlated with variants in JAK2 (Arber et al, 2016). Although musculoskeletal symptoms are not part of the myelofibrosis diagnostic criteria, myelofibrosis patients that received ruxolitinib showed significant improvement of muscle mass over a six-month longitudinal study (Lucijanic et al, 2021). These clinical results align with our overall model that IL-6 and Stat inhibitors could inhibit changes to muscle performance induced by the Upd3/IL-6 brain-muscle signaling axis, and prevent muscle atrophy associated with muscle disuse.…”

Section: Discussionmentioning

confidence: 99%

Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance

Yang¹,

Tian

An³

2020

Preprint

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SummaryThe Coronavirus Disease 2019 (COVID-19) pandemic has caused millions of deaths and will continue to exact incalculable tolls worldwide. While great strides have been made toward understanding and combating the mechanisms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, relatively little is known about the individual SARS-CoV-2 proteins that contribute to pathogenicity during infection and that cause neurological sequela after viral clearance. We used Drosophila to develop an in vivo model that characterizes mechanisms of SARS-CoV-2 pathogenicity, and found ORF3a adversely affects longevity and motor function by inducing apoptosis and inflammation in the nervous system. Chloroquine alleviated ORF3a induced phenotypes in the CNS, arguing our Drosophila model is amenable to high throughput drug screening. Our work provides novel insights into the pathogenic nature of SARS-CoV-2 in the nervous system that can be used to develop new treatment strategies for post-viral syndrome.HighlightsSARS-CoV-2 ORF3a is pathogenic in the nervous system.ORF3a induces cell death, inflammation, and lysosome dysfunction.Chloroquine protects against ORF3a induced CNS distress and lysosome dysfunction.

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Section: Discussionmentioning

confidence: 99%

Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance

Yang¹,

Tian

An³

2020

Preprint

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“…19 It was also reported that earlier commencement of ruxolitinib in MF improves muscle mass. 20 Despite the fact that the majority of our cohort had highrisk disease (54.0%), only one patient underwent allogeneic HSCT. The plausible explanation for low levels of transplant referral includes various considerations for HSCT, such as patient age, insurance coverage, donor availability, financial constraint, and challenging logistic issue.…”

Section: Discussionmentioning

confidence: 89%

The Sarawak Myelofibrosis (SaMy) experience: Demographics and outcome of myelofibrosis patients in Sarawak, Malaysia

Tang,

Leong,

Wong

et al. 2023

SAGE Open Medicine

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Introduction: Myelofibrosis is a rare disease. There is currently no published data reporting the demographics and outcome of myelofibrosis patients in Malaysia. We aimed to study the demographics, clinical characteristics, and outcome of our patients in Sarawak. Materials and methods: This non-interventional, retrospective, and multi-center study was conducted on secondary data of medical records collected at four Sarawak Public Hospitals. All adult myelofibrosis patients diagnosed between January 2001 and December 2021 were included. Results: A total of 63 patients (male 31) with myelofibrosis were included—47 (74.6%) primary and 16 (25.4%) secondary myelofibrosis. Eleven had antecedent polycythaemia vera, whereas five transformed from essential thrombocythaemia. The combined annual incidence rate was 0.182 per 100,000 population. The period prevalence per 100,000 population over the entire study duration was 2.502. The median age was 59.0 years (33.0–93.0). Majority had high-risk (34/63(54.0%)) and intermediate-2 risk disease (19/63(30.2%)). JAK2V617F mutation was identified in 52 patients (82.5%), followed by CALR mutation in 6 (9.5%) and negative for both mutations in 5 (7.9%). Hydroxyurea was used as first-line therapy in 41/63 (65.1%), followed by interferon (8/63(12.7%)) and ruxolitinib (4/63(6.3%)). Out of 46 patients who received second-line therapy, 18 (39.1%) were switched to ruxolitinib and 9 (19.6%) to interferon. The median age of survival for overall patients was 6.8 years. The use of ruxolitinib in myelofibrosis patients showed a better overall 5-year survival compared to the no ruxolitinib arm, despite no statistical significance ( p = 0.34). Patients who had good performance status had lower hazard of death than patients who had poor performance status (high-risk (95% confidence intervals): 0.06(0.013–0.239), p < 0.001). Patients with intermediate risk disease had better overall survival compared to those in high-risk group (95% confidence intervals): 0.24(0.082–0.695), p = 0.009). Conclusion: This registry provides a real-world overview of myelofibrosis patients in our state and highlights the key insight into the unmet clinical need.

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“…The association between skeletal muscle mass and blood cell counts has also been reported in other myeloid malignancies. Improved muscle mass has been shown to be associated with increased hemoglobin levels and less disease progression in patients with myelofibrosis treated with ruxolitinib [ 28 ]. These relationships may be affected by a complex interplay of various factors, including energy metabolism, blood metabolism, iron metabolism, and, possibly, unmeasured variables affecting muscle and hematopoietic function.…”

Section: Discussionmentioning

confidence: 99%

Impact of Skeletal Muscle Depletion on Patients with Myelodysplastic Syndrome Treated with Azacitidine

Takada,

Nakamura,

Kaneda

et al. 2024

Hematology Reports

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Background: Azacitidine (AZA) is the standard treatment for patients with high-risk myelodysplastic syndromes (MDS). The impact of skeletal muscle depletion (SMD), which is associated with outcomes of hematological malignancies, on the clinical course of MDS patients treated with AZA was investigated. Methods: This retrospective, observational study included 50 MDS patients treated with AZA. Muscle mass was evaluated using the skeletal muscle index (SMI), which is the area of muscle mass at the third lumbar vertebra on CT images divided by the square of the height. Results: Of the enrolled patients, 39 were males, and their median age was 69.5 years. Twenty-seven (20 male and 7 female) patients showed SMD. The median survival was 13.4 months in the SMD group and 15.2 months in the non-SMD group, with no significant difference and no significant association between the response rate or severe non-hematological toxicities and the presence of SMD. By contrast, grade 3–4 anemia and thrombocytopenia were significantly more frequent in the SMD group than in the non-SMD group. SMD was associated with severe anemia and thrombocytopenia in MDS patients treated with AZA. Conclusion: Reduced skeletal muscle mass may predict severe hematological toxicity in MDS patients treated with AZA.

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Ruxolitinib treatment improves muscle mass in patients with myelofibrosis

Cited by 11 publications

References 3 publications

Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance

Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance

The Sarawak Myelofibrosis (SaMy) experience: Demographics and outcome of myelofibrosis patients in Sarawak, Malaysia

Impact of Skeletal Muscle Depletion on Patients with Myelodysplastic Syndrome Treated with Azacitidine

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