Original scientific paper
https://doi.org/10.18054/pb.v127i3-4.37864
Analysis of mitochondrial function and antioxidant capacity in JAK2 V617F-positive chronic myeloproliferative neoplasms
Ivona Arić Zrna
; University Hospital Dubrava, Zagreb, Croatia
Marko Lucijanić
; University Hospital Dubrava, Zagreb, Croatia
Branimir Gizdić
; University Hospital Dubrava, Zagreb, Croatia
Mia Nižetić Gović
; University Hospital Dubrava, Zagreb, Croatia
Rajko Kušec
; University Hospital Dubrava, Zagreb, Croatia
Ana Livun
; University Hospital Dubrava, Zagreb, Croatia
Marina Korolija
; University Hospital Dubrava, Zagreb, Croatia
*
* Corresponding author.
Abstract
Background and purpose: The JAK2 V617F mutation, found in the majority of chronic myeloproliferative neoplasms (MPNs), leads to constitutive JAK-STAT pathway activation, driving cell proliferation and increased production of reactive oxygen species (ROS). Mitochondrial dysfunction and oxidative stress are implicated in MPN pathogenesis. In the present study, we aimed to elucidate mitochondrial functionality and patterns of antioxidant and electron transport chain gene expression in patients with JAK2 V617F-positive myeloproliferative neoplasms.
Materials and methods: The study included 66 JAK2 V617F-positive MPN patients and 30 healthy controls. All participants completed the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) to assess symptom burden. MitoTracker™ (MT) and Nonyl Acridine Orange (NAO) probes were used for flow cytometric assessment of mitochondrial membrane potential and mass, based on mean fluorescence intensity (MFI). Total RNA was isolated, and expression of SOD2, CAT, SIRT3 and MT-ND1 was quantified by qPCR using TaqMan™ probes and normalized to ACTB using the ΔΔCt method.
Results: The MT/NAO MFI ratio, reflecting mitochondrial membrane potential relative to mass, was significantly reduced in JAK2 V617F-positive patients compared to controls (p = 0.003). Antioxidant gene expression (SOD2, SIRT3, CAT) and MT-ND1, a key regulator of oxidative phosphorylation, were markedly downregulated in patients (p < 0.001).
Conclusions: We show for the first time that patients with the JAK2 V617F mutation exhibit mitochondrial dysfunction, characterized by increased mitochondrial mass, decreased mitochondrial membrane potential, and impaired oxidative phosphorylation and antioxidant defense. To elucidate the potential genetic background of the observed mitochondrial dysfunction, mitochondrial genes should be assessed by sequencing.
Keywords
mitochondrial function; antioxidant enzymes; JAK2 V617F; myeloproliferative neoplasms
Hrčak ID:
347129
URI
Publication date:
13.5.2026.
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