However, this is not efficacious in all HR-MDS-MSCs; samples HR261 and HR325, which were obtained from patients in < 1 year before disease transformation leading to death were only partially responsive to AZA therapy.
MDS-MSCs that fail to respond to hypomethylating therapy are associated with patients with rapid adverse disease transformation and this further suggests that MDS-MSCs may be an integral part of disease progression and have prognostic value as well as potential as a therapeutic target.
To cope with increased metabolic stress, malignant cells often reprogram their biochemical pathways to enable rapid uptake and breakdown of nutrients, thus contributing to disease transformation, maintenance, and progression (Hanahan and Weinberg, 2011; Ward and Thompson, 2012).
Multiple types of cancer are marked by drastic changes to TCA cycle enzymes, which result in characteristic metabolic and epigenetic changes that are correlated with disease transformation and progression.
Recent findings show that multiple cycle enzymes are either mutated or deregulated in a broad spectrum of cancer, resulting in characteristic metabolic and epigenetic changes that are correlated with disease transformation and progression.
Homozygously mutated genes in aUPD regions that function in the initiation and progression of cancer may be associated with tumor type or subtype [8], [27], risk of disease transformation [9], patient's survival time [9], [28].
Other studies confirmed the lack of correlation related to JAK2 mutational status and disease transformation.
Additionally, patients having higher Ang-1 expression would have higher chance of disease transformation to AML.
Further understanding of the molecular events leading to disease transformation is being investigated.
Potentially fatal disease complications in PV and ET include disease transformation into myelofibrosis (MF) or acute myeloid leukemia (AML).
