@Article{ecn.2012.0322,
AUTHOR = {Håkon Reikvam, Kimberley Joanne Hatfield, Hanne Fredly, Ina Nepstad, Knut Anders Mosevoll, Øystein Bruserud},
TITLE = {The angioregulatory cytokine network in human acute myeloid leukemia – from leukemogenesis via remission induction to stem cell transplantation},
JOURNAL = {European Cytokine Network},
VOLUME = {23},
YEAR = {2012},
NUMBER = {4},
PAGES = {140--153},
URL = {http://www.techscience.com/ECN/v23n4/65687},
ISSN = {1952-4005},
ABSTRACT = {Acute myeloid leukemia (AML) is characterized by bone marrow accumulation of immature leukemic
blast cells. Conventional AML treatment includes induction chemotherapy to achieve disease control, followed by
consolidation therapy with conventional chemotherapy or allogeneic/autologous stem cell transplantation (allo/autoSCT)
to eradicate residual disease. Even younger patients receiving the most intensive treatment have a median,
long-term, AML-free survival of only 45-50%, highlighting the need for new treatment strategies. The important
role of the bone marrow cytokine network during disease development and treatment is suggested by several
observations, including: (i) the increased microvascular density (MVD) in leukemic bone marrow, (ii) experimental
evidence of cytokine-mediated crosstalk between leukemic and microvascular endothelial cells, (iii) the prognostic
impact of angioregulatory cytokine levels both in patients receiving conventional chemotherapy and allo-SCT, and
(iv) the experimental evidence for an antileukemic effect of cytokine inhibition in human AML. Several cytokines
are constitutively released by human AML cells, including interleukins, chemokines, vascular endothelial growth
factor (VEGF), hepatocyte growth factor (HGF) and angiopoietins. However, the cytokine system constitutes a
functional, interacting network, and recent evidence suggests that analysis of serum cytokine profiles rather than
the analysis of single cytokines should be used for prognostic evaluation of AML patients. We will discuss the role
of angioregulatory cytokines in leukemogenesis, including their direct effects on the leukemic cells, as well as their
indirect contribution to leukemogenesis through angioregulation and crosstalk between leukemic and neighboring
stromal cells. We shall also discuss the possibility of targeting angioregulatory cytokines as a part of the treatment
strategy in leukemia.},
DOI = {10.1684/ecn.2012.0322}
}