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Figure 2. The diagram illustrates the different mechanisms acquired by the GC-resistant subclones and leading to GC-resistance, i.e., LOH, GR mutations, and a failure to up-regulate GR levels in response to GC. While 11/37 resistant CEM-C7H2 subclones were shown to be affected by both, mutations of the GR and loss of one allele, thereby leaving the cell with no functional GR at all, none of the resistant PreB subclones revealed complete loss of functional GR. LOH without mutations occurred in 26/37 resistant CEM-C7H2 subclones compared with 2/30 instances in the resistant PreB697 lines. Similarly, also resulting in only one WT GR allele, 3/30 PreB697 lines carried GR mutations of one allele. In most PreB697 subclones (25/30) neither mutations nor LOH could account for the deficient GR up-regulation. Hence, although GR autoinduction deficiency was a conserved feature in all GC-resistant subclones from both ALL models, different molecular mechanisms resulted in this phenomenon.
