8 However, the detailed mechanism of conversion to more malignant clones in the presence of EBV is unknown.
It has even been suggested that the more malignant clones harbouring genetic defects such as mutations in p53 might be selected by hypoxia for the survival (Royds et al, 1998).
Tumor-bearing C.IL6Myc mice exhibited paraprotein 'M-spikes' upon serum protein electrophoresis, indicating either the presence of a single, greatly expanded clone of Ig-producing PCs (see, for example, the pronounced extragradient in lane 4) or the coexistence of two or more malignant cell clones prior to the emergence of the dominant clone (lanes 2, 5 and 8).
DLBCLs are relatively heterogeneous and, in a few cases, can switch their genetic or immunohistochemical phenotype and transform into other lymphomas or carry more than one malignant clone [ 19].
In contrast, ruxolitinib treatment in myelofibrosis leads to a much more modest reduction in the size of the malignant clone (Cervantes et al, 2013), and there is not yet clear evidence that it alters progression to acute myeloid leukaemia.
Tumour cell adaptation allows survival and gives rise to heterogeneity and selection of resistant clones, consequently resulting in a more malignant phenotype (Semenza, 2003).
A hallmark of myeloid cancers is the ability of the malignant clone to evolve into multiple, frequently more aggressive subclones, as a result of either the natural history of the disease or the selective pressure of chemotherapy.
In order to isolate individual aptamers that may distinguish the more malignant U87MG phenotype, a panel of 71 sequences was cloned from the pool G14, and aptamers grouped in families based on their primary sequence similarity (Fig. 2).
Among C57BL/6 lymphoma cells progression toward a more malignant phenotype was observed in TB6-3 cells, and in their derived clones, after several in vitro passages.
Similarly, the modern Multi-Stage Model of Carcinogenesis argues that cancer incidence is driven by the occurrence of successive cancer driver mutations in individual clones, leading to a step-wise acquisition of progressively more malignant phenotypes [ 7- 10].
