TY - JOUR

T1 - Revisiting Circulating Extracellular Matrix Fragments as Disease Markers in Myelofibrosis and Related Neoplasms

AU - Hasselbalch, Hans Carl

AU - Junker, Peter

AU - Skov, Vibe

AU - Kjær, Lasse

AU - Knudsen, Trine A.

AU - Larsen, Morten Kranker

AU - Holmström, Morten Orebo

AU - Andersen, Mads Hald

AU - Jensen, Christina

AU - Karsdal, Morten A.

AU - Willumsen, Nicholas

N1 - Publisher Copyright: © 2023 by the authors.

PY - 2023

Y1 - 2023

N2 - Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) arise due to acquired somatic driver mutations in stem cells and develop over 10–30 years from the earliest cancer stages (essential thrombocythemia, polycythemia vera) towards the advanced myelofibrosis stage with bone marrow failure. The JAK2V617F mutation is the most prevalent driver mutation. Chronic inflammation is considered to be a major pathogenetic player, both as a trigger of MPN development and as a driver of disease progression. Chronic inflammation in MPNs is characterized by persistent connective tissue remodeling, which leads to organ dysfunction and ultimately, organ failure, due to excessive accumulation of extracellular matrix (ECM). Considering that MPNs are acquired clonal stem cell diseases developing in an inflammatory microenvironment in which the hematopoietic cell populations are progressively replaced by stromal proliferation—“a wound that never heals”—we herein aim to provide a comprehensive review of previous promising research in the field of circulating ECM fragments in the diagnosis, treatment and monitoring of MPNs. We address the rationales and highlight new perspectives for the use of circulating ECM protein fragments as biologically plausible, noninvasive disease markers in the management of MPNs.

AB - Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) arise due to acquired somatic driver mutations in stem cells and develop over 10–30 years from the earliest cancer stages (essential thrombocythemia, polycythemia vera) towards the advanced myelofibrosis stage with bone marrow failure. The JAK2V617F mutation is the most prevalent driver mutation. Chronic inflammation is considered to be a major pathogenetic player, both as a trigger of MPN development and as a driver of disease progression. Chronic inflammation in MPNs is characterized by persistent connective tissue remodeling, which leads to organ dysfunction and ultimately, organ failure, due to excessive accumulation of extracellular matrix (ECM). Considering that MPNs are acquired clonal stem cell diseases developing in an inflammatory microenvironment in which the hematopoietic cell populations are progressively replaced by stromal proliferation—“a wound that never heals”—we herein aim to provide a comprehensive review of previous promising research in the field of circulating ECM fragments in the diagnosis, treatment and monitoring of MPNs. We address the rationales and highlight new perspectives for the use of circulating ECM protein fragments as biologically plausible, noninvasive disease markers in the management of MPNs.

KW - circulating extracellular matrix (ECM) proteins

KW - hyaluronan

KW - laminin

KW - MPN

KW - MPNs

KW - myeloproliferative neoplasms

KW - neoepitopes

KW - procollagen type I C-terminal propeptide (PICP)

KW - protein fingerprints

KW - serum procollagen III N-terminal propeptide (PIIINP)

KW - type IV collagen

U2 - 10.3390/cancers15174323

DO - 10.3390/cancers15174323

M3 - Review

C2 - 37686599

AN - SCOPUS:85170245883

VL - 15

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 17

M1 - 4323

ER -