Patients with acute myeloid leukemia can be subclassified based on the constitutive cytokine release of the leukemic cells; the possible clinical relevance and the importance of cellular iron metabolism

Abstract

Subclassification of AML patients based on the constitutive cytokine release may be clinically relevant and a part of a low-risk (i.e. chemosensitive) AML cell phenotype.

Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia

“…All samples in our study were cryopreserved by using the same standardized technique and without any difference in storage time between our two patient subsets. Furthermore, both our present in vivo chemotherapy study and several previous patient studies have demonstrated that the biological characteristics of the total hierarchical AML cell population reflect the risk of relapse (i.e., the chemosensitivity), both with regard to genetic abnormalities as well as constitutive in vitro cytokine release, global and stem cell gene expression profiles, epigenetic characteristics and intracellular pathway activation [12][13][14][66][67][68][69][70][71][72]. Thus, even though leukemic stem cells are regarded as responsible for AML relapse [73], biological characteristics associated with relapse risk are also reflected in the total AML cell population.…”

“…Upregulated iron transport and vesicle proteins were enriched in REL_FREE patients. In an independent study, AML patients with high constitutive cytokine release showed increased mRNA expression of proteins involved in intracellular iron homeostasis and molecular trafficking [66]. Interestingly, the overall survival after intensive chemotherapy was significantly higher for high-release compared with low-release AML patients.…”

Two acute myeloid leukemia patient subsets are identified based on the constitutive PI3K-Akt-mTOR signaling of their leukemic cells; a functional, proteomic, and transcriptomic comparison

“…The prognostic impact of global mRNA profiles as well as selected mRNA profiles (e.g. leukemic stem cell profiles) [31,198], epigenetic regulation [199], single molecular markers detected at the mRNA [200] or protein level [34,201], and constitutive cytokine release profiles ___________________________________________________________________________ [202] has been demonstrated through analysis of the total AML cell population.…”

“… In vivo evaluation through observation of bone marrow blast counts 17 days after the start of induction therapy, as well as the use of minimal residual disease (MRD) estimation by flow cytometry during consolidation therapy, is also based on evaluation of common AML cell characteristics [202].…”

Circulating cytokines and small molecules follow distinct expression patterns in acute myeloid leukaemia

“…Their roles in the pathophysiology at different stages of carcinogenesis are increasingly recognised ( Hanahan and Weinberg, 2000 ). Although deregulated expression of circulating analytes in AML is well documented ( Van Etten, 2007 ; Seruga et al , 2008 ; Tsimberidou et al , 2008 ; Kornblau et al , 2010 ; Brenner et al , 2017 ), considerable baseline variability of inter- and intra-assay plasma analytes levels are reported in AML ( Kornblau et al , 2010 ; Kupsa et al , 2014 ). In addition, plasma baselines for some analytes that are biomarkers for other cancers have not been previously reported in AML.…”