Identification of Two Critically Deleted Regions within Chromosome Segment 7q35-q36 in EVI1 Deregulated Myeloid Leukemia Cell Lines

An De Weer,Yves Benoit,Bruce Poppe,Nadine Van Roy,Pieter Van Vlierberghe,Frank Speleman,Anne De Paepe,Lucien Noens,Björn Menten,Marjan Petrick,Robrecht De Bock,Sarah Vergult,Anita Brandstaetter

doi:10.1371/journal.pone.0008676

Abstract

Chromosomal rearrangements involving the EVI1 proto-oncogene are a recurrent finding in myeloid leukemias and are indicative of a poor prognosis. Rearrangements of the EVI1 locus are often associated with monosomy 7 or cytogenetic detectable deletions of part of 7q. As EVI1 overexpression alone is not sufficient to induce leukemia, loss of a 7q tumour suppressor gene might be a required cooperating event. To test this hypothesis, we performed high-resolution array comparative genomic hybridization analysis of twelve EVI1 overexpressing patients and three EVI1 deregulated cell lines to search for 7q submicroscopic deletions. This analysis lead to the delineation of two critical regions, one of 0.39 Mb on 7q35 containing the CNTNAP2 gene and one of 1.33 Mb on chromosome bands 7q35–q36 comprising nine genes in EVI1 deregulated cell lines. These findings open the way to further studies aimed at identifying the culprit EVI1 implicated tumour suppressor genes on 7q.

Highlights

Chromosomal rearrangements involving chromosome band 3q26, such as translocations with various partner chromosomes or inversions of chromosome 3 are a recurrent finding in myeloid leukemias [1]
We performed high-resolution array comparative genomic hybridization (CGH) analysis to search for 7q submicroscopic deletions in EVI1 deregulated leukemia patients in order to identify candidate 7q tumour suppressor genes
We identified several submicroscopic 7p and 7q deletions in EVI1 overexpressing patients and cell lines (Table 3 and Figure 1) including two critically deleted regions on 7q35–q36 in EVI1 deregulated cell lines

Summary

Introduction

Chromosomal rearrangements involving chromosome band 3q26, such as translocations with various partner chromosomes or inversions of chromosome 3 are a recurrent finding in myeloid leukemias [1]. We performed high-resolution array comparative genomic hybridization (CGH) analysis to search for 7q submicroscopic deletions in EVI1 deregulated leukemia patients in order to identify candidate 7q tumour suppressor genes. Three EVI1 rearranged cell lines, Kasumi-3, MUTZ-3 and UCSD-AML1 were included in the study [7,8].

Results

Conclusion