JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms

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  • Christina Schjellerup Eickhardt-Dalbøge
  • Henrik V. Nielsen
  • Kurt Fuursted
  • Christen Rune Stensvold
  • Lee O’Brien Andersen
  • Berit Lilje
  • Larsen, Morten Kranker
  • Lasse Kjær
  • Sarah Friis Christensen
  • Trine Alma Knudsen
  • Vibe Skov
  • Anders Lindholm Sørensen
  • Ellervik, Christina
  • Lars Rønn Olsen
  • Jens Jørgen Elmer Christensen
  • Xiaohui Chen Nielsen
  • Hasselbalch, Hans K
  • Anna Cäcilia Ingham
Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (MF) are myeloproliferative neoplasms (MPN). Inflammation is involved in the initiation, progression, and symptomology of the diseases. The gut microbiota impacts the immune system, infection control, and steady-state hematopoiesis.

We analyzed the gut microbiota of 227 MPN patients and healthy controls (HCs) using next-generation sequencing. We expanded our previous results in PV and ET patients with additional PV, pre-MF, and MF patients which allowed us to compare MPN patients collectively, MPN sub-diagnoses, and MPN mutations (separately and combined) vs. HCs (N = 42) and compare within MPN sub-diagnoses and MPN mutation.

MPN patients had a higher observed richness (median, 245 [range, 49–659]) compared with HCs (191.5 [range, 111–300; p = .003]) and a lower relative abundance of taxa within the Firmicutes phylum; for example, Faecalibacterium (6% vs. 14%, p < .001). The microbiota of CALR-positive patients (N = 30) resembled that of HCs more than that of patients with JAK2V617F (N = 177). In JAK2V617F-positive patients, only minor differences in the gut microbiota were observed between MPN sub-diagnoses, illustrating the importance of this mutation.

The gut microbiota in MPN patients differs from HCs and is driven by JAK2V617F, whereas the gut microbiota in CALR patients resembles HCs more.
BogserieEuropean Journal of Haematology
Udgave nummer5
Sider (fra-til)776-787
Antal sider12
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
Most importantly we are grateful to all the participants of the study. We are also grateful for the help of the doctors at the Department of Hematology, Zealand University Hospital, Roskilde Denmark, participating in including patients to the study. Furthermore, we express gratitude towards the lab technicians at the Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen for the help with the analysis, and the medical lab technicians at the Regional Department of Clinical Microbiology, University Hospital of Region Zealand, Slagelse, Denmark for the help with dividing the samples. Thank you to Mette Grymer Jensen (Medical and Research Secretary) for your help with the organizing and collection of stools samples. This work was founded by the Region Zealand Foundation for Health Research, the Department of Bacteria, Parasites & Fungi, Statens Serum Institut, Copenhagen, Denmark, and the Danish Cancer Society. CE is partly funded by the Laboratory Medicine Endowment Fund of Boston Children's Hospital.

Publisher Copyright:
© 2024 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.

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