3q26/ EVI1 rearrangements in myeloid hemopathies: a cytogenetic review

Abstract

The EVI1 gene, located in chromosomal band 3q26, is a transcription factor that has stem cell-specific expression pattern and is essential for the regulation of self-renewal of hematopoietic stem cells. It is now recognized as one of the dominant oncogenes associated with myeloid leukemia. EVI1 overexpression is associated with minimal to no response to chemotherapy and poor clinical outcome. Several chromosomal rearrangements involving band 3q26 are known to induce EVI1 overexpression. They are mainly found in acute myeloid leukemia and blastic phase of Philadelphia chromosome-positive chronic myeloid leukemia, more rarely in myelodysplastic syndromes. They include inv(3)(q21q26), t(3;3)(q21;q26), t(3;21)(q26;q22), t(3;12)(q26;p13) and t(2;3)(p15-23;q26). However, many other chromosomal rearrangements involving 3q26/EVI1 have been identified. The precise molecular event has not been elucidated in the majority of these chromosomal abnormalities and most gene partners remain unknown.

Review: Aberrant EVI1 expression in acute myeloid leukaemia

“…Similar to inv (3)/t(3;3) AML, in AML with t(2;3)(p15-22;26), t(3;7)(q26; q21), t(3;6)(q26;q25) and t(3;17)(q26;q22), EVI1 mRNA is expressed rather than MDS1-EVI1 or a fusion protein (De Braekeleer et al, 2015). In rearrangements involving 3q26, such as t(3;21) and t(3;12), which are relatively frequently found in AML, EVI1 activation is due to gene fusion, resulting in the chimeric transcription factors Runt-Related Transcription Factor 1 (RUNX1) -EVI1 or Ets Variant 6 (ETV6) -EVI1, respectively (De Braekeleer et al, 2015). In rearrangements involving 3q26, such as t(3;21) and t(3;12), which are relatively frequently found in AML, EVI1 activation is due to gene fusion, resulting in the chimeric transcription factors Runt-Related Transcription Factor 1 (RUNX1) -EVI1 or Ets Variant 6 (ETV6) -EVI1, respectively (De Braekeleer et al, 2015).…”

“…However, overexpression of EVI1 has been shown to act as an independent adverse prognostic marker for complete remission (CR), overall-(OS), relapse free-(RFS) and event-free (EFS) survival in AML, i.e., irrespective of the presence of 3q26 rearrangements (Barjesteh van Waalwijk van Doorn-Khosrovani et al, 2003;Lugthart et al, 2008;Groschel et al, 2010). Frequencies of monosomy 7/deletion 7q (-7/del(7q)), 11q23 abnormalities (11q23) or complex karyotype (Complex; three or more chromosomal abnormalities) in AML with various abnormalities involving EVI1 De Braekeleer et al, 2015). In multivariate models, including cytogenetic risk, age, white blood cell count (WBC) and NPM1 mutant/FLT3 wild type geno- Table II.…”

“…Expression of human EVI1, located at chromosome 3 band q26, is affected by recurrent chromosomal translocations in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) De Braekeleer et al, 2015). Furthermore, 3q26 aberrations are observed in patients with chronic myeloid leukaemia (CML) that progress to the acute blast phase (Johansson et al, 2002).…”

“…MDS1-EVI1 results from alternative splicing of the third exon of MDS1 Table I. Characteristics and frequencies of abnormalities involving EVI1 in 3q AML, 3q MDS, AML and MDS (Stars:case reports) De Braekeleer et al, 2015). EVI1 overexpression* Transcription factor Fig 1B).…”

“…Characteristics and frequencies of abnormalities involving EVI1 in 3q AML, 3q MDS, AML and MDS (Stars:case reports)De Braekeleer et al, 2015).…”