CSF3R T618I co-occurs with mutations of splicing and epigenetic genes and with a new PIM3 truncated fusion gene in chronic neutrophilic leukemia

J Menezes,H Makishima,J P Maciejewski,S Álvarez,O Graña,A Dopazo,J C Cigudosa,D G Pisano,M Trujillo,I Gomez,F Acquadro,G Gómez-López

doi:10.1038/bcj.2013.55

Abstract

CSF3R T618I co-occurs with mutations of splicing and epigenetic genes and with a new PIM3 truncated fusion gene in chronic neutrophilic leukemia

Highlights

Mutations in CSF3R have been recently defined as the common genetic event in patients with myeloid neoplasms, including the rare entity known as chronic neutrophilic leukemia (CNL),[1,2,3] becoming a potentially useful biomarker for diagnosing and therapy target.[4]
To improve our understanding of the genes involved in the pathogenesis of CNL, whole-exome sequencing (WES) was performed on matched tumor and oral mucosa cell samples from the patient
These mutations, which affect distinct residues in CSF3R as compared with CNL, are frequently associated with mutations in the ASXL1 gene and have a poor prognostic impact on overall and acute myeloid leukemia (AML)-free survival. These data indicate that CNL genome had a combination of few mutations with a pattern of cooperation with a strong biological relationship among genes and categories, similar to AML.[7]. Along this line of cooperating mutations on epigenetic genes, we found in our CNL patient mutated copies of ASXL1 and TET2 genes

Summary

LETTER TO THE EDITOR

Blood Cancer Journal (2013) 3, e158; doi:10.1038/bcj.2013.55; published online 8 November 2013. Kosmider et al.,[3] very recently, showed that CSF3R somatic mutations can be identified in B4% of chronic myelomonocytic leukemias These mutations, which affect distinct residues in CSF3R as compared with CNL, are frequently associated with mutations in the ASXL1 gene and have a poor prognostic impact on overall and acute myeloid leukemia (AML)-free survival. We previously described mutations of this gene in myelodysplastic syndrome (MDS).[8] As this gene is located in the 7q region, a frequently deleted chromosomal region in myeloid leukemias,[9] we decided to investigate whether a critical deletion or a loss of heterozygosity (LOH) affecting this genomic region was present in the patient To study this phenomenon, we interrogate our WES data for the LOH across the whole genome of the sample. We identified a chimeric transcript involving the PIM3 and SCO2 genes (both were located on 22q13.33), which was the result of an

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AUTHOR CONTRIBUTIONS

Findings

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