Low expression of MDS1-EVI1-like-1 (MEL1) and EVI1-like-1 (EL1) genes in favorable-risk acute myeloid leukemia.
OBJECTIVE
The expression of an MDS1-EVI1-like-1 (MEL1) gene is reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with translocation t(1;3)(p36;q21). MEL1 (at chromosome band 1p36.3) is thought to be transcriptionally activated as a result of juxtaposition to the RPN1 gene at 3q21. It is not known whether MEL1 expression is restricted to cases with this particular translocation.


METHODS
Using real-time polymerase chain reaction, we measured MEL1 expression levels, normal bone marrow, and distinct blood cell fractions in 162 de novo AML patients. We also investigated the existence of an EVI1-like gene (EL1) by applying the same method. The existence of these transcripts was confirmed by Northern blot analysis.


RESULTS
MEL1 expression was detected in 87% (141/162) of de novo AML patients. The EL1 transcript also was detected in the majority of the patients. EL1 expression levels highly correlated with MEL1 expression levels in AML cases. Variable MEL1/EL1 expression levels were observed. However, all the patients with favorable-risk karyotypes, i.e., with t(15;17), t(8;21), or inv(16), showed low MEL1/EL1 expression levels. Expression analysis of MEL1/EL1 compared with MDS1-EVI1/EVI1 in distinct normal marrow or blood cell fractions revealed that 1) all four gene products are expressed in CD34(+) progenitor cell fractions; 2) both MEL1 and EVI1 are turned down in neutrophils and monocytes/macrophages; while 3) MDS1-EVI1 and EL1 remain expressed in mature blood cell fractions.


CONCLUSIONS
Our data suggest that simultaneous low MEL1/EL1 expression in AML is abnormal and that favorable disease is highly associated with this abnormal phenotype.
Institute of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands.
Sahar
S
Barjesteh van Waalwijk van Doorn-Khosrovani
Claudia
C
Erpelinck
Bob
B
Löwenberg
Ruud
R
Delwel
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001853:Bone Marrow / Q000737:chemistry; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics; D005260:Female; D006412:Hematopoietic Stem Cells / Q000737:chemistry; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000209:etiology* / Q000378:metabolism; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C416371:PRDM16 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors