Abstract

Genetic aberrations contribute to acute myeloid leukemia (AML). However, half of AML cases do not contain the well-known aberrations detectable mostly by cytogenetic analysis, and these cases are classified as normal karyotype AML. Different outcomes of normal karyotype AML suggest that this subgroup of AML could be genetically heterogeneous. But lack of genetic markers makes it difficult to further study this subgroup of AML. Using paired-end RNAseq method, we performed a transcriptome analysis in 45 AML cases including 29 normal karyotype AML, 8 abnormal karyotype AML and 8 AML without karyotype informaiton. Our study identified 134 fusion transcripts, all of which were formed between the partner genes adjacent in the same chromosome and distributed at different frequencies in the AML cases. Seven fusions are exclusively present in normal karyotype AML, and the rest fusions are shared between the normal karyotype AML and abnormal karyotype AML. CIITA, a master regulator of MHC class II gene expression and truncated in B-cell lymphoma and Hodgkin disease, is found to fuse with DEXI in 48% of normal karyotype AML cases. The fusion transcripts formed between adjacent genes highlight the possibility that certain such fusions could be involved in oncological process in AML, and provide a new source to identify genetic markers for normal karyotype AML.

Highlights

  • Acute myeloid leukemia (AML) is a major type of leukemia, with estimated 13,780 new cases and 10,200 death in the United States in 2012 (American Cancer Society, 2012, http://www. cancer.org/Research/CancerFactsFigures/CancerFactsFigures/ cancer-facts-figures-2012)

  • Eight abnormal karyotype AML cases and eight AML cases without karyotype data were included for the study

  • Each fusion was distributed at different frequencies among the AML cases, with the highest one of 57 fusions detected in a normal karyotype AML case (#25, Table S1)

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Summary

Introduction

Acute myeloid leukemia (AML) is a major type of leukemia, with estimated 13,780 new cases and 10,200 death in the United States in 2012 (American Cancer Society, 2012, http://www. cancer.org/Research/CancerFactsFigures/CancerFactsFigures/ cancer-facts-figures-2012). Amplification, inversion, insertion, and deletion, are wellknown to contribute to leukemia [1], and multiple recurrent genetic aberrations including t(9;11), inv(16), t(15;17) and t(8;21), have been identified in AML. These aberrations disrupt the normal structure of the affected genes and form fusion genes. Half of AML cases do not contain the known genetic aberrations detectable by cytogenetic techniques [3,4,5,6]. These AML cases are classified into a subgroup named normal karyotype

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