JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms

Christina Schjellerup Eickhardt-Dalbøge; Henrik V Nielsen; Kurt Fuursted; Christen Rune Stensvold; Lee O' Brien Andersen; Berit Lilje; Morten Kranker Larsen; Lasse Kjaer; Sarah Friis Christensen; Trine Alma Knudsen; Vibe Skov; Anders Lindholm Sørensen; Christina Ellervik; Lars Rønn Olsen; Jens Jørgen Elmer Christensen; Xiaohui Chen Nielsen; Hans Carl Hasselbalch; Anna Cäcilia Ingham

doi:10.1111/ejh.14169

JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms

Christina Schjellerup Eickhardt-Dalbøge^*
, Henrik V Nielsen
, Kurt Fuursted
, Christen Rune Stensvold
, Lee O' Brien Andersen
, Berit Lilje
, Morten Kranker Larsen
, Lasse Kjaer
, Sarah Friis Christensen
, Trine Alma Knudsen
, Vibe Skov
, Anders Lindholm Sørensen
, Christina Ellervik
, Lars Rønn Olsen
, Jens Jørgen Elmer Christensen
, Xiaohui Chen Nielsen
, Hans Carl Hasselbalch
, Anna Cäcilia Ingham

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: The gut microbiota in MPN patients differs from HCs and is driven by JAK2V617F, whereas the gut microbiota in CALR patients resembles HCs more.

Original language	English
Pages (from-to)	776-787
Number of pages	12
Journal	European Journal of Haematology
Volume	112
Issue number	5
Early online date	16 Jan 2024
DOIs	https://doi.org/10.1111/ejh.14169
Publication status	Published - May 2024

Funding

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.

Funders
Statens Serum Institut
Region Sjælland
Statens Serum Institut
Danish Cancer Society

Keywords

Essential thrombocythemia
Gut microbiota
Myeloproliferative neoplasms
Polycythemia vera
Primary myelofibrosis

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10.1111/ejh.14169

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Eickhardt-Dalbøge, C. S., Nielsen, H. V., Fuursted, K., Stensvold, C. R., Andersen, L. O. B., Lilje, B., Larsen, M. K., Kjaer, L., Christensen, S. F., Knudsen, T. A., Skov, V., Sørensen, A. L., Ellervik, C., Olsen, L. R., Christensen, J. J. E., Nielsen, X. C., Hasselbalch, H. C., & Ingham, A. C. (2024). JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms. European Journal of Haematology, 112(5), 776-787. https://doi.org/10.1111/ejh.14169

@article{ecdae9540cc9477aa73b3fc422fb9dd2,

title = "JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms",

abstract = "BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSION: The gut microbiota in MPN patients differs from HCs and is driven by JAK2V617F, whereas the gut microbiota in CALR patients resembles HCs more.",

keywords = "Essential thrombocythemia, Gut microbiota, Myeloproliferative neoplasms, Polycythemia vera, Primary myelofibrosis",

author = "Eickhardt-Dalb{\o}ge, \{Christina Schjellerup\} and Nielsen, \{Henrik V\} and Kurt Fuursted and Stensvold, \{Christen Rune\} and Andersen, \{Lee O' Brien\} and Berit Lilje and Larsen, \{Morten Kranker\} and Lasse Kjaer and Christensen, \{Sarah Friis\} and Knudsen, \{Trine Alma\} and Vibe Skov and S{\o}rensen, \{Anders Lindholm\} and Christina Ellervik and Olsen, \{Lars R{\o}nn\} and Christensen, \{Jens J{\o}rgen Elmer\} and Nielsen, \{Xiaohui Chen\} and Hasselbalch, \{Hans Carl\} and Ingham, \{Anna C{\"a}cilia\}",

note = "{\textcopyright} 2024 The Authors. European Journal of Haematology published by John Wiley \& Sons Ltd.",

year = "2024",

month = may,

doi = "10.1111/ejh.14169",

language = "English",

volume = "112",

pages = "776--787",

journal = "European Journal of Haematology",

issn = "0902-4441",

publisher = "John Wiley \& Sons Inc.",

number = "5",

}

Eickhardt-Dalbøge, CS, Nielsen, HV, Fuursted, K, Stensvold, CR, Andersen, LOB, Lilje, B, Larsen, MK , Kjaer, L , Christensen, SF , Knudsen, TA , Skov, V, Sørensen, AL, Ellervik, C, Olsen, LR, Christensen, JJE, Nielsen, XC , Hasselbalch, HC & Ingham, AC 2024, 'JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms', European Journal of Haematology, vol. 112, no. 5, pp. 776-787. https://doi.org/10.1111/ejh.14169

TY - JOUR

T1 - JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms

AU - Eickhardt-Dalbøge, Christina Schjellerup

AU - Nielsen, Henrik V

AU - Fuursted, Kurt

AU - Stensvold, Christen Rune

AU - Andersen, Lee O' Brien

AU - Lilje, Berit

AU - Larsen, Morten Kranker

AU - Kjaer, Lasse

AU - Christensen, Sarah Friis

AU - Knudsen, Trine Alma

AU - Skov, Vibe

AU - Sørensen, Anders Lindholm

AU - Ellervik, Christina

AU - Olsen, Lars Rønn

AU - Christensen, Jens Jørgen Elmer

AU - Nielsen, Xiaohui Chen

AU - Hasselbalch, Hans Carl

AU - Ingham, Anna Cäcilia

PY - 2024/5

Y1 - 2024/5

N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSION: The gut microbiota in MPN patients differs from HCs and is driven by JAK2V617F, whereas the gut microbiota in CALR patients resembles HCs more.

AB - BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSION: The gut microbiota in MPN patients differs from HCs and is driven by JAK2V617F, whereas the gut microbiota in CALR patients resembles HCs more.

KW - Essential thrombocythemia

KW - Gut microbiota

KW - Myeloproliferative neoplasms

KW - Polycythemia vera

KW - Primary myelofibrosis

U2 - 10.1111/ejh.14169

DO - 10.1111/ejh.14169

M3 - Article

C2 - 38226781

SN - 0902-4441

VL - 112

SP - 776

EP - 787

JO - European Journal of Haematology

JF - European Journal of Haematology

IS - 5

ER -

JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms

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Keywords

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