Speaker
Description
The Philadelphia-chromosome-negative myeloproliferative neoplasms (MPNs) are slowly developing haematological malignancies characterised by an overproduction of blood cells. Chronic inflammation is associated with the diseases and suggested to play an important role in disease initiation and progression as well as being a consequence of the diseases.
In the DALIAH trial, treatment-naïve MPN patients were treated with either Hydroxyurea (HU) or low dose interferon-$\alpha$ (IFN-$\alpha$) and followed for up to five years \cite{knudsen_final_2023}. Both HU and IFN-$\alpha$ are commonly used treatments for MPN. On top of their cytoreductive effects, IFN-$\alpha$ is a potent immunostimulatory cytokine, while HU has been shown to decrease the level of pro-inflammatory cytokines and the neutrophil-to-lymphocyte ratio in sickle cell disease patients \cite{zahran_effect_2020}.
With a mechanism-based, nonlinear ordinary differential equation model, we investigate the role of inflammation in MPN disease progression and response to treatment. The model includes stem cell, progenitor cell, and mature cell
compartments of wild-type and mutated hematological cells with a nonlinear
negative feedback from the mature to the stem cell compartments.
By comparing the mechanism-based model to longitudinal measurements of mature blood cell counts, variant allele frequency of the MPN driver mutation \textit{JAK2}V617F, and cytokines of the patients enrolled in the DALIAH trial, we aim to identify a signature of inflammatory mediators with prognostic impact.
Bibliography
@article{zahran_effect_2020,
title = {Effect of {Hydroxyurea} {Treatment} on the {Inflammatory} {Markers} {Among} {Children} {With} {Sickle} {Cell} {Disease}},
volume = {26},
issn = {1076-0296, 1938-2723},
doi = {10.1177/1076029619895111},
language = {en},
urldate = {2026-03-12},
journal = {Clinical and Applied Thrombosis/Hemostasis},
author = {Zahran, Asmaa M. and Nafady, Asmaa and Saad, Khaled and Hetta, Helal F. and Abdallah, Alam-Eldin M. and Abdel-Aziz, Safwat M. and Embaby, Mostafa M. and Abo Elgheet, Amir M. and Darwish, Sanaa F. and Abo-Elela, Mohamed Gamil M. and Elhoufey, Amira and Elsayh, Khalid I.},
month = jan,
year = {2020},
pages = {1076029619895111},
}
@article{knudsen_final_2023,
title = {Final {Analysis} of the {Daliah} {Trial}: {A} {Randomized} {Phase} {III} {Trial} of {Interferon}-$\alpha$ {Versus} {Hydroxyurea} in {Patients} with {MPN}},
volume = {142},
issn = {0006-4971, 1528-0020},
shorttitle = {Final {Analysis} of the {Daliah} {Trial}},
doi = {10.1182/blood-2023-173127},
language = {en},
number = {Supplement 1},
urldate = {2026-03-12},
journal = {Blood},
author = {Knudsen, Trine Alma and Hansen, Dennis Lund and Ocias, Lukas Frans and Bjerrum, Ole and Brabrand, Mette and Christensen, Sarah Friis and Eickhardt-Dalbøge, Christina Schjellerup and Ellervik, Christina and El Fassi, Daniel and Frederiksen, Mikael and Kjær, Lasse and Kristensen, Thomas Kielsgaard and Kruse, Torben A. and Larsen, Morten Kranker and Mourits-Andersen, Torben and Möller, Sören and Overgaard, Ulrik Malthe and Severinsen, Marianne Tang and Skov, Vibe and Sørensen, Anders Lindholm and Stentoft, Jesper and Starklint, Jørn and De Stricker, Karin and Thomassen, Mads and Larsen, Thomas S. and Hasselbalch, Hans C.},
month = nov,
year = {2023},
pages = {746--746},
}
