Recently, autosomal dominant germline ETV6 mutations were discovered in families with inherited thrombocytopenia and a propensity to develop hematological malignancy, unequivocally demonstrating a role for ETV6 in leukemogenesis.
Heterogeneity in the breakpoints in balanced rearrangements involving band 12p13 in hematologic malignancies identified by fluorescence in situ hybridization: TEL (ETV6 ) is involved in only one half.
TEL is a new member of the ETS family of transcription factors which is rearranged in a number of hematologic malignancies with translocations involving chromosome band 12p13.
FISH analyses and loss of heterozygosity studies have delineated a commonly deleted region in hematological malignancies flanked by ETV6 and CDKN1B on chromosome 12p12.3.
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.
The translocation results in the fusion of two known genes, ETV6/TEL(12p13) and AML1(21q22), both of which have been shown to be involved in other hematological malignancies.
To characterize the incidence, clinical features and genetics of ETV6-ABL1 leukemias, representing targetable kinase-activating lesions, we analyzed 44 new and published cases of ETV6-ABL1-positive hematologic malignancies [22 cases of acute lymphoblastic leukemia (13 children, 9 adults) and 22 myeloid malignancies (18 myeloproliferative neoplasms, 4 acute myeloid leukemias)].
Variants in ETV6, which encodes a transcription repressor of the E26 transformation-specific family, have recently been reported to be responsible for inherited thrombocytopenia and hematologic malignancy.
The ETV6 gene encodes an ETS family transcription factor that is involved in a myriad of chromosomal rearrangements found in hematological malignancies and other neoplasms.
The human TEL gene is involved in several 12p13 chromosomal abnormalities present in various human hematological malignancies, the most frequent being the t(12;21)(p13;q22), specific for childhood acute lymphoblastic leukemia.
ETV6-ABL1 fusion is a rare but recurrent genetic aberration found in various hematologic malignancies involving both the lymphoid and myeloid lineage, but to the best of our knowledge, CMML is an exceptionally rare presentation of ETV6-ABL1 rearranged neoplasm.
Two known genes map within the critically deleted region of 12p: TEL, the gene encoding a new member of the ETS family of transcription factors, which is rearranged in a variety of hematological malignancies; and KIP1, the gene encoding the cyclin-dependent kinase inhibitor p27.
This case reiterates the importance of correlating morphologic and phenotypic findings with the results of cytogenetic analysis to avoid errors in diagnosing hematologic neoplasms and highlights the rare association of B-cell non-Hodgkin lymphoma with aberrations of TEL.
HDAC9 interacts and co-localizes in vivo with a number of transcriptional repressors and co-repressors, including TEL and N-CoR, whose functions have been implicated in the pathogenesis of hematological malignancies.
Alterations of the short arm of chromosome 12 (12p) occur in various hematologic malignancies and ETV6 and CDKN1B, which are located on 12p, have been implicated as leukemogenic genes of interest.
The TEL/AML1 fusion does not occur in children with AML and suggests that the TEL/AML1 rearrangement is restricted in pediatric hematologic malignancy to B lineage ALL.