Leukemia with t(1;12)(q21;p13) was previously described in a 5-year-old boy with acute myeloblastic leukemia (AML-M2) who exhibited a novel ETV6-aryl hydrocarbon receptor nuclear translocator (ARNT) fusion protein.
ETV6/RUNX1 (E/R) (also known as TEL/AML1) is the most frequent gene fusion in childhood acute lymphoblastic leukemia (ALL) and also most likely the crucial factor for disease initiation; its role in leukemia propagation and maintenance, however, remains largely elusive.
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.
Additionally, the ETV6-RUNX1 fusion was found to encode putative neoepitopes in a high proportion (69.6%) of the pediatric leukemia harboring this fusion.
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.
Although first described less than four years ago, the TEL/AML1 story is an excellent example of how close collaboration between physicians and molecular biologists is mandatory for achieving general insights into the molecular pathogenesis of leukemia and for further improvements in diagnosis and in monitoring response to chemotherapy.
Although the function of TTL is yet to be elucidated, our findings will provide another insight into the molecular pathogenesis of leukemia having ETV6-involving translocations.
Analysis of four different types of ETV6/ARG transcripts previously identified in the AML-M3 leukemia cell line HT93A suggest that ETV6 HLH domain is required for oncogenic activity.
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.
Because many chromosomal alterations in leukemia are associated with distinct cell surface phenotypes, we investigated whether there was an association seen between surface marker expression and the TEL-AML1 rearrangement.
Breakpoints in general displayed similar complexity of duplications, deletions, and insertions to other common pediatric leukemia translocations (TEL-AML1, MLL-AF4, PML-RARA, CBFB-MYH11) that we and others have analyzed.
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.
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.