The modification of this translocation may lead to reducing effects of the fusion gene's damaging and the dosage compensation related to ETV6 and RUNX1 genes and subsequently reduce the effects of leukemia.
CRKL is tightly linked to leukemia via its binding partners BCR-ABL and TEL-ABL, upregulated in multiple types of human cancers, and induce cancer cell proliferation and invasion.
We suggest that germline aberrations resulting in monoallelic expression of <i>ETV6</i> contribute to leukemia susceptibility, whereas more severe functional deficiency of ETV6 is required for developing THC5.
Care for individuals with ETV6-related thrombocytopenia and leukemia predisposition includes genetic counseling, treatment or prevention of excessive bleeding and surveillance for the development of hematologic malignancy.
A 4-log-stage linearity of R2 ≥ 99.81% and a sensitivity of one leukemia associated ETV6-RUNX1 mutant DNA copy in a background of 100 000 wild-type DNA copies are achieved.
The prenatal origin of the rearrangement confirms that ETV6-ABL1 is not sufficient to cause overt leukemia, even when combined with the 2 novel fusions.
Additionally, the ETV6-RUNX1 fusion was found to encode putative neoepitopes in a high proportion (69.6%) of the pediatric leukemia harboring this fusion.
The most frequent chromosomal changes in subgroups divided according to WHO classification independent of treatment protocol and leukemia subtype were hyperdiploidy in 36 patients (with ≥50 chromosomes in 23 patients, with 47-49 chromosomes 13 patients) followed by translocation t(12;21) with ETV6/RUNX1 fusion detected by FISH in 18 (22%) patients.
As few <i>ETV6-RUNX1</i> carriers develop precursor B-cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor.
We show here for the first time that LPXN is a fusion partner of ETV6 and present evidence indicating that ETV6-LPXN plays a crucial role in leukemia progression through enhancing the response to G-CSF and CXCL12.
All together, our study defined a unique lncRNA expression signature associated with ETV6/RUNX1-positive BCP-ALL and identified lnc-RTN4R-1 and lnc-NKX2-3-1 as lncRNAs that might be functionally implicated in the biology of this prevalent subtype of human leukemia.
Further investigation into the clinical and biological significance of elevated MN1 expression in TEL-AML1(positive) leukemia might provide insight into additional molecular mechanisms contributing to B-ALL and may lead to improved treatment options for patients.