Abstract

The identification of effective signatures is crucial to predict the prognosis of acute myeloid leukemia (AML). The investigation aimed to identify a new signature for AML prognostic prediction by using the three-gene expression (octamer-binding transcription factor 4 (OCT4), POU domain type 5 transcription factor 1B (POU5F1B) and B-cell-specific Moloney murine leukemia virus integration site-1 pseudogene 1 (BMI1P1). The expressions of genes were obtained from our previous study. Only the specimens in which three genes were all expressed were included in this research. A three-gene signature was constructed by the multivariate Cox regression analyses to divide patients into high-risk and low-risk groups. Receiver operating characteristic (ROC) analysis of the three-gene signature (area under ROC curve (AUC) = 0.901, 95% CI: 0.821–0.981, P<0.001) indicated that it was a more valuable signature for distinguishing between patients and controls than any of the three genes. Moreover, white blood cells (WBCs, P=0.004), platelets (PLTs, P=0.017), percentage of blasts in bone marrow (BM) (P=0.011) and complete remission (CR, P=0.027) had significant differences between two groups. Furthermore, high-risk group had shorter leukemia-free survival (LFS) and overall survival (OS) than low-risk group (P=0.026; P=0.006), and the three-gene signature was a prognostic factor. Our three-gene signature for prognosis prediction in AML may serve as a prognostic biomarker.

Highlights

  • Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by infiltration of blood, bone marrow (BM) and other tissues by clonal, proliferative, abnormally differentiated and poor morphology, cytochemistry, immunophenotype, cytogenetics and molecular abnormalities of leukemia population

  • The data from the common specimens of the three genes were picked for further study, including 15 healthy donors as normal controls and 88 de novo AML patients who were diagnosed by the French–American–British (FAB) [20] and World Health Organzation (WHO) classifications [21]

  • As we discovered from the previous data, patients in AML with higher BMI 1 pseudogene 1 (BMI1P1) and POU domain type 5 transcription factor 1B (POU5F1B) expression had significantly better overall survival (OS) than lower expression

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Summary

Introduction

Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by infiltration of blood, bone marrow (BM) and other tissues by clonal, proliferative, abnormally differentiated and poor morphology, cytochemistry, immunophenotype, cytogenetics and molecular abnormalities of leukemia population. It is a highly heterogeneous disease that may be resulted from gene mutation or overexpression [1–3]. Despite 75–85% of patients can achieve complete remission (CR) after induction chemotherapy, the 5-year survival is still less than 50% [4]. The median survival of patients over 65 years old is less than 1 year, and only 20% of patients survive for more than 2 years [5]. In order to make better treatment decision, more effective signatures are needed [6]. Developments in molecular genetics, in cytogenetic results and molecular abnormalities, stimulated the identification of prognostic signatures of AML [7]

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