M Jia1, H-Z Zhao1, H-P Shen1, Y-P Cheng1, Z-B Luo1, S-S Li1, J-Y Zhang1, Y-M Tang1. 1. Division of Hematology-oncology, Children's Hospital of Zhejiang University School of Medicine, Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou, China.
Abstract
INTRODUCTION: Lymphoid enhancer-binding factor-1 (LEF1) is a target gene and central mediator of the Wnt signaling pathway. High LEF1 expression has been reported as a prognostic marker in several types of hematologic malignancies of adult patients. METHODS: In this study, LEF1 expression was analyzed by real-time polymerase chain reaction (PCR) in 122 children with newly diagnosed ALL treated on the China NPCAC97 protocols. Patients' samples were dichotomized at the median value of control group and divided into LEF1(low) and LEF1(high) groups. RESULTS: The LEF1 mRNA levels in patients with ALL were significantly higher than those of normal controls, and the LEF1 levels were dramatically decreased following induction therapy. In addition, LEF1(high) patients had lower white blood cell (WBC) count at diagnosis and lower minimal residual disease (MRD) levels at the time of complete remission as compared to LEF1(low) patients. Finally, our studies showed that high LEF1 expression is associated with favorable CR rate and overall survival (OS) in childhood ALL (5-year OS: LEF1(high) 92% vs. LEF1(low) 73%, P = 0.009). High LEF1 level was associated with a favorable relapse-free survival in standard-risk patients and also related to a better OS within the subgroup of patients with BCR-ABL-negative ALL. CONCLUSION: Overexpression of LEF1 is a favorable prognostic factor in childhood ALL. The prognostic impact of LEF1 may assist treatment stratification and suggest the need of alternative regimens.
INTRODUCTION:Lymphoid enhancer-binding factor-1 (LEF1) is a target gene and central mediator of the Wnt signaling pathway. High LEF1 expression has been reported as a prognostic marker in several types of hematologic malignancies of adult patients. METHODS: In this study, LEF1 expression was analyzed by real-time polymerase chain reaction (PCR) in 122 children with newly diagnosed ALL treated on the China NPCAC97 protocols. Patients' samples were dichotomized at the median value of control group and divided into LEF1(low) and LEF1(high) groups. RESULTS: The LEF1 mRNA levels in patients with ALL were significantly higher than those of normal controls, and the LEF1 levels were dramatically decreased following induction therapy. In addition, LEF1(high) patients had lower white blood cell (WBC) count at diagnosis and lower minimal residual disease (MRD) levels at the time of complete remission as compared to LEF1(low) patients. Finally, our studies showed that high LEF1 expression is associated with favorable CR rate and overall survival (OS) in childhood ALL (5-year OS: LEF1(high) 92% vs. LEF1(low) 73%, P = 0.009). High LEF1 level was associated with a favorable relapse-free survival in standard-risk patients and also related to a better OS within the subgroup of patients with BCR-ABL-negative ALL. CONCLUSION: Overexpression of LEF1 is a favorable prognostic factor in childhood ALL. The prognostic impact of LEF1 may assist treatment stratification and suggest the need of alternative regimens.
Authors: M A ElBaiomy; S Aref; M El Zaafarany; Sara Atwa; Tamer Akl; Wafaa El-Beshbishi; Shaimaa El-Ashwah; L Ibrahim; M El-Ghonemy Journal: Adv Hematol Date: 2019-12-18
Authors: Tiffany Carr; Stephanie McGregor; Sheila Dias; Mihalis Verykokakis; Michelle M Le Beau; Hai-Hui Xue; Mikael Sigvardsson; Elizabeth T Bartom; Barbara L Kee Journal: Front Immunol Date: 2022-03-18 Impact factor: 7.561