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.
Although multiple mutations within JAK2, which abrogate the function of JH2 and sustain JAK2 activation, are widely observed in hematological malignancies, comparable mutations have not been detected in solid tumors.
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.
Myeloproliferative neoplasms (MPN) are clonal hematological malignancies that are frequently -associated with an acquired somatic mutation in JAK2 (JAK2V617F).
The gain of function mutation JAK2-V617F is very frequently found in myeloproliferative neoplasms (MPNs) and is strongly implicated in pathogenesis of these and other hematological malignancies.
We also discuss the role of JAK inhibitors for treatment of CSF3RT618I-mutated chronic neutrophilic leukemia and hematologic malignancies with rearranged JAK2 gene.
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.
The human JAK2 gene is mainly targeted by two types of genetic lesions that play roles in the pathogenesis of hematologic malignancies: intragenic mutations and chromosomal translocations.
Ruxolitinib is an oral JAK1 and JAK2 inhibitor that has recently been approved for the treatment of myelofibrosis and has been tested against other hematologic 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)].
Decreased PLK4 protein expression due to promoter hypermethylation was negatively correlated with JAK2 overexpression, a common occurrence in hematological malignancies.