Biological drivers of clinical phenotype in myelofibrosis.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
30
09
2022
accepted:
14
11
2022
revised:
10
11
2022
pubmed:
27
11
2022
medline:
8
2
2023
entrez:
26
11
2022
Statut:
ppublish
Résumé
Myelofibrosis (MF) is a myeloproliferative disorder that exhibits considerable biological and clinical heterogeneity. At the two ends of the disease spectrum are the myelodepletive or cytopenic phenotype and the myeloproliferative phenotype. The cytopenic phenotype has a high prevalence in primary MF (PMF) and is characterized by low blood counts. The myeloproliferative phenotype is typically associated with secondary MF (SMF), mild anemia, minimal need for transfusion support, and normal to mild thrombocytopenia. Differences in somatic driver mutations and allelic burden, as well as the acquisition of non-driver mutations further influences these phenotypic differences, prognosis, and response to therapies such as JAK2 inhibitors. The outcome of patients with the cytopenic phenotype are comparatively worse and frequently pose a challenge to treat given the inherent exacerbation of cytopenias. Recent data indicate that an innate immune deregulated state that hinges on the myddosome-IRAK-NFκB axis favors the cytopenic myelofibrosis phenotype and offers opportunity for novel treatment approaches. We will review the biological and clinical features of the MF disease spectrum and associated treatment considerations.
Identifiants
pubmed: 36434065
doi: 10.1038/s41375-022-01767-y
pii: 10.1038/s41375-022-01767-y
pmc: PMC9898039
doi:
Substances chimiques
Janus Kinase 2
EC 2.7.10.2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
255-264Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2022. The Author(s).
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