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Reprimo(RPRM) is a novel tumor suppressor. However, the expression and molecular function ofRPRMin pediatric acute myeloid leukemia (AML) is still unknown. We observed hypermethylation of theRPRMpromoter in 8/11 leukemia cell lines and in 44.8% (47/105) of pediatric AML samples compared with 6.7% (2/30) of control samples. Bisulfite genomic sequencing analysis showed that theRPRMpromoter was methylated in the majority of AML samples (66.2–83.1%), whereasRPRMwas almost unmethylated in normal bone marrow samples (20.0–27.7%). Kaplan–Meier survival analysis revealed poor survival outcomes in samples withRPRMpromoter methylation (p< 0.001). Proliferation of AML cells was inhibited in a dose-dependent manner (p< 0.05) afterRPRMoverexpression with lentivirus transfection. Apoptosis was up-regulated inRPRM-overexpressing AML cells. Real-time polymerase chain reaction array analysis revealed 50 dysregulated genes that might be implicated in apoptosis ofRPRM-induced AML cells.RPRMmay be a putative tumor suppressor in pediatric AML. [ABSTRACT FROM AUTHOR]

Data on serial evaluation of immunoglobulins (Ig) in pediatric AML is lacking. From April 2010 to May 2011, 45 consecutive patients with AML aged 1-18 years were prospectively enrolled along with nine healthy controls. Ig were assessed at diagnosis, post-induction, post-consolidation, 3 and 6 months follow-up and relapse. At diagnosis, Ig levels were significantly higher in patients than in healthy controls. Patienths with gum hypertrophy had low Ig levels (IgG, p = 0.007; IgA, p = 0.003; IgM, p = 0.06). Baseline Ig did not correlate with complete remission (CR). Patients who relapsed had a lower baseline IgA level than those in continuous CR (169 ± 94 g/dL vs. 310 ± 177 g/dL, p = 0.019). Patients with a low baseline IgA level (less than median) had inferior disease-free-survival (DFS) on multivariate analysis ( p = 0.048). Post-induction, IgM ( p < 0.001) and IgA ( p = 0.048) were significantly reduced as compared to their baseline values. On serial follow-up in patients who were in continuous CR, there was a significant decrease in IgA from post-induction until 6 months after treatment completion. This is the first study to evaluate the trend of humoral immunity in sequential pediatric patients with AML. Our study demonstrates that in pediatric AML, baseline Ig were higher than in controls. Gum hypertrophy was observed in patients with low Ig (IgA and IgG) levels. Relatively lower baseline IgA predicted disease relapse and inferior DFS. On serial follow-up, IgA significantly decreased in those who continued to stay in CR but not in patients who relapsed, suggesting an association of IgA with leukemogenesis. [ABSTRACT FROM AUTHOR]