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2015 ; 2015
(ä): 869242
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Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms
#MMPMID26543328
Hoermann G
; Greiner G
; Valent P
Mediators Inflamm
2015[]; 2015
(ä): 869242
PMID26543328
show ga
The term myeloproliferative neoplasms (MPN) refers to a heterogeneous group of
diseases including not only polycythemia vera (PV), essential thrombocythemia
(ET), and primary myelofibrosis (PMF), but also chronic myeloid leukemia (CML),
and systemic mastocytosis (SM). Despite the clinical and biological differences
between these diseases, common pathophysiological mechanisms have been identified
in MPN. First, aberrant tyrosine kinase signaling due to somatic mutations in
certain driver genes is common to these MPN. Second, alterations of the bone
marrow microenvironment are found in all MPN types and have been implicated in
the pathogenesis of the diseases. Finally, elevated levels of proinflammatory and
microenvironment-regulating cytokines are commonly found in all MPN-variants. In
this paper, we review the effects of MPN-related oncogenes on cytokine expression
and release and describe common as well as distinct pathogenetic mechanisms
underlying microenvironmental changes in various MPN. Furthermore, targeting of
the microenvironment in MPN is discussed. Such novel therapies may enhance the
efficacy and may overcome resistance to established tyrosine kinase inhibitor
treatment in these patients. Nevertheless, additional basic studies on the
complex interplay of neoplastic and stromal cells are required in order to
optimize targeting strategies and to translate these concepts into clinical
application.
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