Acute lymphoblastic leukemia/lymphoblastic lymphoma

T-cell acute lymphoblastic leukemia (T-ALL) affects about 15% of pediatric patients and 25% of adult patients of total ALL cases. It is an aggressive tumor characterized by the accumulation of multiple genomic mutations and chromosomal aberrations, such as frequently chromosomal translocations, that bring to the formation of many in-frame fusion genes encoding the respective chimeric and oncogenic proteins (Atak et al., 2013). Among all these chromosomal aberrations it was found also the fusion gene 5 EEF1G / 3 OOEP deriving by the genomic translocation and fusion of a part of OOEP gene, situated on chromosome 6, with a portion of EEF1G gene, instead located on chromosome 11. This leads to the know but not still well-characterized translocation t(6;11)(q13;q12) EEF1G/OOEP.

There is no evidence of impact of the EEF1G/OOEP fusion gene on the tumor behavior and also its contribute in the prognosis of acute lymphoblastic leukemia/lymphoblastic lymphoma is still unknown.

The result of chromosomal anomaly is the novel fusion gene 5 EEF1G / 3 OOEP. Atak and colleagues (Atak et al., 2013) found its DNA in T-cell acute lymphoblastic leukemia (T-ALL), but there are no data or evidence about its mRNA and its protein. So, in this review, with the use of various tools and software will be predicted the possible transcript and also the probable protein. However, the data collected are hypothesis and have to be experimental verified.

The fusion gene 5 EEF1G / 3 OOEP was found in T-cell acute lymphoblastic leukemia (T-ALL) (Atak et al., 2013) and it derives by the genomic translocation t(6;11)(q13;q12) EEF1G/OOEP, i.e. by fusion of a part of OOEP gene, situated on chromosome 6, with a portion of EEF1G gene, instead located on chromosome 11. In particular, the fusion interests part of exon 8 and exon 7 of EEF1G that result fused with a portion of the second intron sequence, i.e. intron 2-3, of the OOEP-202, an alternative splicing form of OOEP that contains also the ribosomal protein L39 pseudogene 3, alias RPL39P3 (https://www.ensembl.org). By the analysis of the sequences reported in Ensembl appears that the portion of the OOEP gene that is fused with EEF1G is really a portion of RPL39P3 pseudogene.

There is no evidence about the mRNA of the EEF1G/OOEP fusion gene. However, with bioinformatic tools it is possible to predict its sequence and characterizing it. It seems to be formed by both the non-coding 5UTR and 3UTR and a coding sequence (CDS). The CDS is among 221 and 374 nt with a length of 154 nt and it is apparently protein-coding. It was chosen the longer codifying sequence of the 5->3 strand in that the sequence offers more reading possibilities (https://www.ncbi.nlm.nih.gov/orffinder/).

There is no evidence about the protein of the EEF1G/OOEP fusion gene. However, with INSILICO and ORFFINDER tools (http://insilico.ehu.es/translate/index2.php; https://www.ncbi.nlm.nih.gov/orffinder/) is possible to predict the protein sequence of the EEF1G/OOEP mRNA. The protein counts 51 amino acids with a molecular mass of 6,41 kDa and a theoretical pI of 12.55 (https://web.expasy.org/cgi-bin/protparam/ protparam). Surprisingly a perfect sequence homology with ribosomal L39 protein (RPL39) is noted by BlastP analysis and can be found the ribosomal L39 putative domain (https://blast.ncbi.nlm.nih.gov/Blast.cgi). The post-translational modifications are unknown.

There is no evidence not only of the protein but also of its localization. However, the predicted sub-cellular localization for the protein is cytoplasm (http://linux1.softberry.com/cgi-bin/programs/proloc/protcompan.pl).

It is unclear the role in oncogenesis of the translocation t(6;11)(q13;q12) EEF1G/OOEP and there is no evidence about its effective transcription and/or translation. Perhaps the EEF1G/OOEP fusion gene plays a regulatory role or it is instead effectively translated into a functional protein, that by bioinformatic analysis seems to be RPL39-like protein and that deriving from RPL39P3 pseudogene. It was demonstrated that RPL39 plays a role in metaplastic breast cancer where shows an oncogenic activity through the increase of the inducible nitric oxide synthase ( NOS2). Moreover, it was evidenced that a high RPL39 and iNOS expression are associated with a reduction in patient overall survival (Dave et al., 2017), so the abnormal translocation t(6;11)(q13;q12) EEF1G/OOEP could be linked with an increase of RPL39 levels in acute lymphoblastic leukemia/lymphoblastic lymphoma cancer cells by the translation of its pseudogene RPL39P3. In addition, some authors found high expression of RPL39P3 in human colon cancer LIM1863 cell line (Chen et al., 2016).
However, these are only hypothesis and the truly oncogenic potential of EEF1G/OOEP in proliferation and cancer aggressiveness needs to be better elucidated.

EEF1G/OOEP