New fusion transcripts identified in normal karyotype acute myeloid leukemia

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

New Fusion Transcripts Identified in Normal Karyotype Acute Myeloid Leukemia

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.</p

New Fusion Transcripts Identified in Normal Karyotype Acute Myeloid Leukemia

<div><p>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. <em>CIITA</em>, a master regulator of MHC class II gene expression and truncated in B-cell lymphoma and Hodgkin disease, is found to fuse with <em>DEXI</em> 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.</p> </div

Fusion transcript information.

<p>A. Fusion transcripts identified in different types of AML. B. Validated fusion transcripts identified in normal karyotype AML.</p

Long-range PCR results.

<p>A. Summary of the results from 11 fusion candidates. B. Size distribution of the amplified genomic DNA fragments.</p

Validation of sense and antisense fusion transcripts by strand-specific RT-PCR.

<p>A. Summary for RNA samples from 8 myeloid cell lines. B. <i>CIITA-DEXI</i> sense and antisense fusion transcripts detected in myeloid cell lines and AML samples. +: positive control with beta-actin; -: netative control without RNA templates.</p

NFATC3-PLA2G15 fusion.

<p>The fusion is formed between upstream gene <i>NFATC3</i> and downstream gene <i>PLA2G15</i> in 3′-5′ tail to head orientation. In this fusion, amino acid V (GTC) is shared at the fusion point (G from <i>NFATC3</i> and TC from <i>PLA2G15</i>). A. Wild-type NFATC3 protein sequence; B. Wild-type PLA2G15 protein sequence; C. NFATC3-PLA2G15 fusion protein sequences. The bold V residue marks the fusion junction.</p

<i>CIITA-DEXI</i> fusion.

<p>A. CIITA-involved protein-protein interaction network. B. Mapping and validation of <i>CIITA-DEXI</i> fusion. Three <i>CIITA-DEXI</i> fusions were detected. In the fusion, <i>CIITA</i> preserved the coding exone till the stop codon but losed its 3′ untranslated region. This fusion was detected by 23 paired-end RNAseq sequences and validated by Sanger sequencing.</p