A scoring system based on fusion genes to predict treatment outcomes of the non-acute promyelocytic leukemia pediatric acute myeloid leukemia.

Background: Fusion genes are considered to be one of the major drivers behind cancer initiation and progression. Meanwhile, non-acute promyelocytic leukemia (APL) pediatric patients with acute myeloid leukemia (AML) in children had limited treatment efficacy. Hence, we developed and validated a simple clinical scoring system for predicting outcomes in non-APL pediatric patients with AML. Method: A total of 184 non-APL pediatric patients with AML who were admitted to our hospital and an independent dataset (318 patients) from the TARGET database were included. Least absolute shrinkage and selection operation (LASSO) and Cox regression analysis were used to identify prognostic factors. Then, a nomogram score was developed to predict the 1, 3, and 5 years overall survival (OS) based on their clinical characteristics and fusion genes. The accuracy of the nomogram score was determined by calibration curves and receiver operating characteristic (ROC) curves. Additionally, an internal verification cohort was used to assess its applicability. Results: Based on Cox and LASSO regression analyses, a nomogram score was constructed using clinical characteristics and OS-related fusion genes (CBFß::MYH11, RUNX1::RUNX1T1, KMT2A::ELL, and KMT2A::MLLT10), yielded good calibration and concordance for predicting OS of non-APL pediatric patients with AML. Furthermore, patients with higher scores exhibited worse outcomes. The nomogram score also demonstrated good discrimination and calibration in the whole cohort and internal validation. Furthermore, artificial neural networks demonstrated that this nomogram score exhibits good predictive performance. Conclusion: Our model based on the fusion gene is a prognostic biomarker for non-APL pediatric patients with AML. The nomogram score can provide personalized prognosis prediction, thereby benefiting clinical decision-making.

Prognostic significance of the tumor suppressor protein p53 gene in childhood acute lymphoblastic leukemia.

The tumor suppressor protein p53 (TP53) gene is associated with various types of cancer; however, little is known about TP53 expression in patients with childhood acute lymphoblastic leukemia (ALL). The aim of the present study was to investigate the prognostic value of TP53 expression in childhood ALL. To achieve this, TP53 mRNA levels of 146 children with ALL and 23 child donors with idiopathic thrombocytopenic purpura were determined by reverse transcription-quantitative PCR. Relapse-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. The results demonstrated that TP53 mRNA level in patients with ALL was higher compared with that in the ITP donors (P=0.019). Patients with highly-expressed TP53 exhibited lower percentages of peripheral blood blast, higher platelet counts and inferior complete remission rates compared with patients with low expression of TP53. Survival analyses revealed that high TP53 expression was associated with poor OS and RFS in childhood ALL (P=0.018 and P=0.028, respectively) and was an independent prognostic factor in multivariate analysis for poor RFS (P<0.001) and OS (P<0.001). In conclusion, high TP53 expression is associated with poor outcomes and may be used as a molecular prognostic marker to be incorporated into an improved risk classification system for childhood ALL.

Overexpression of SET and MYND domain-containing protein 2 (SMYD2) is associated with poor prognosis in pediatric B lineage acute lymphoblastic leukemia.

High expression of SET and MYND domain-containing protein 2(SMYD2) has been reported as a poor prognostic factor for various types of cancer. However, there are little published data about clinical significance of SMYD2 in children with ALL. We used real-time polymerase chain reaction (PCR) to detect SMYD2 expression in the bone marrow (BM) samples from 134 newly diagnosed children with ALL. Our data showed that children with ALL demonstrated significantly higher SMYD2 expression than control group (p < .001). SMYD2 mRNA expression levels decreased significantly after complete remission. In addition, patients with higher SMYD2 expression had higher white blood cell count (p = .003) and higher percentage of high-risk groups (p = .005). Survival analyses showed that higher SMYD2 expression was associated with worse overall survival and event free survival (EFS) in children with B lineage ALL(B-ALL) and was an independent prognostic factor in multivariate analyses.

Low expression of TET2 gene in pediatric acute lymphoblastic leukemia is associated with poor clinical outcome.

INTRODUCTION: TET2, a member of the Ten-Eleven translocation gene family, catalyzes the conversion of 5-methylcytosine to 5-hydroxymethylcytosine in DNA. Low expression of TET2 has been reported as a prognostic factor for several types of malignancies in adult patients. However, there have been few data on the effect of TET2 mRNA level on the prognosis of children with ALL so far. METHODS: In this study, TET2 expression of samples cryopreserved in the liquid nitrogen from January 1, 2007 through December 31, 2011 was retrospectively analyzed in 136 newly diagnosed ALL patients by real-time polymerase chain reaction (PCR) assay. The patients' samples were divided into two groups by the median value of patients group and divided into TET2 low and TET2 high groups. RESULTS: A total of 136 childhood ALL patients demonstrated lower TET2 expression than control group (P = .038). TET2 mRNA expression levels were correlated with the disease status. In addition, patients with low TET2 expression had lower platelet counts and lower CR rates. Survival analysis showed that low TET2 expression in children with ALL was associated with lower 5-year overall survival (OS) (63% vs 88%, P = .011) and event-free survival (EFS) (60% vs 85%, P = .003). Multivariate analysis revealed that low TET2 expression was an independent poor prognostic factor of OS and EFS. CONCLUSION: Low expression of TET2 in children with ALL is associated with poor prognosis and can be used as a molecular prognostic marker for risk group stratification.