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To explore the differences in the clinical features, treatment responses, and outcomes among children, adolescents, and adults with chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib as first-line therapy. Data from children (0-8 years for girls and 0-10 years for boys), adolescents (9-19 years for girls and 11-19 years for boys), and adults (age ≥ 20 years) with newly diagnosed CML-CP receiving imatinib as first-line therapy between 2006 and 2019 were retrospectively reviewed. In total, 135 children (cohort 1), 189 adolescents (cohort 2), and 658 adults (cohort 3: age 20-39 years, n = 305; cohort 4: age 40-59 years, n = 270; and cohort 5: age 60-83 years, n = 83) were included in this study. When compared with children, adolescents showed a significantly higher white blood cell count (P = 0.033) and basophil percentage in peripheral blood (P = 0.002) and a significantly higher prevalence of splenomegaly (P = 0.004). Both children and adolescents presented with more aggressive clinical features than adults. During median follow-ups of 28 months (range, 3-161 months) in children, 33 months (range, 3-152 months) in adolescents, and 48 months (range, 3-157 months) in adults, multivariate analysis showed that children and adolescents had higher probabilities of achieving complete cytogenetic response, major molecular response, and molecular response

Alternative splicing of the glucocorticoid receptor (GR) gene results in several GR isoforms, we examined their expression (GRα, GRβ, GRγ and GR-P) by real-time RT-PCR in glucocorticoid (GC) sensitive (CEM-C7), GC resistant (CEM-C1) cells and adult acute lymphoblastic leukemia (ALL) patients, to determine the association of GR isoform expression profiles and GC resistance in adult ALL patients. With GC treatment, GR levels in C1 cells showed no obvious changes. In C7 cells, the mRNA levels of GRα, GRβ and GRγ first increased and then decreased, whereas GR-P mRNA had a continued rising trend. C7 cells had a higher GRα/GRγ, lower GRα/GR-P and GRγ/GR-P ratios than C1 cells (P0.01). In adult ALL patients, GRγ mRNA varied in different ALL stages (complete remission CR 15.82 vs. relapsed 8.21 vs. initial 1.93 P0.05). It also did in the ratios between GR isoforms that GRα/GRγ and GRα/GR-P in initial patients were higher than relapsed and CR (P0.05), while GRγ/GR-P in CR was higher than initial and relapsed patients (P0.05). GR-P mRNA in T-ALL patients was much higher than that in B-ALL patients (P0.05). Peripheral blood hemoglobin (HB) was positively correlated with GRα mRNA and GR-P mRNA (P0.05), while white blood cells (WBC) negatively correlated with GRγ mRNA (P0.05). The present study demonstrates that GR autoinduction is more important to GC sensitivity than its basal level expression. GC sensitivity is also significantly correlated with GRα mRNA and mildly associated with GRβ mRNA expression. Both GRγ mRNA and the ratios between GR isoforms (GRα/GRγ, GRα/GR-P and GRγ/GR-P) are correlated with ALL stages. The changes of mRNA expression levels of GRα, GR-P and GRγ may provide valuable information for GC resistance. Peripheral blood HB and WBC affect GR isoform expression.

The expression of glucocorticoid receptor (GR) isoforms has been linked to glucocorticoid (GC) resistance in various diseases treated with GC. However, existing data are conflicting in these diseases, and little information is available regarding immune thrombocytopenia (ITP). To further investigate the role of GR isoforms in GC resistance in adult ITP patients, we measured the mRNA expression of GR isoforms (GRα, GRβ, GRγ, GRp) in peripheral blood mononuclear cells (PBMC) from 54 newly diagnosed ITP patients, including GC-sensitive (GCS) and GC-resistant (GCR) patients and 35 healthy volunteers. The GRα and GRβ proteins in PBMC, nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) in the nucleus were detected by Western blotting. Compared to normal subjects, both GRα and GRβ mRNAs were significantly increased in ITP patients (p < 0.05), while there was no significant difference in the mRNA expression of GRγ and GRp. Compared to GCR patients, the expressions of GRα mRNA and GRα protein were significantly higher in GCS patients (p < 0.05). Moreover, no significant difference in the mRNA expression of the GRβ, GRγ, and GRp isoforms was observed between GCS and GCR patients and the GRβ protein could not be detected. Compared to GCS group, the expression of p65/NF-κB was significantly higher in the GCR group (p < 0.05). Overall, we did not find differences in c-Jun/AP-1 protein expression between GCS and GCR patients. In summary, GC resistance in adult ITP patients is associated with a reduced expression of GRα, which may be related with increased NF-κB. GRβ was very low and may not be involved in GC resistance in adult ITP, warranting further exploration.