Changes

Recurrent TET2 mutation was first reported in myelodysplastic syndrome (MDS) patients with chromosome 4q24 abnormalities. In this cohort ''TET2'' mutations have been observed in 19-26% of patients and are among the most common genetic lesions (Delhommeau et al., 2009; Langemeijer et al., 2009). Cell lineage evidence supports the notion that ''TET2'' mutations occur very early during disease evolution (Itzykson et al., 2013a; Langemeijer et al., 2009). ''TET2'' mutations are overrepresented in samples with normal cytogenetics (Bejar et al., 2011). Mutations in ''EZH2'' occur in as many as 35% of ''TET2''-mutated MDS (Muto et al., 2013). There is no impact of ''TET2'' mutations on overall survival, but their presence may predict response to hypomethylating agents (Bejar et al., 2011; Itzykson et al., 2011).

Recurrent TET2 mutation was first reported in myelodysplastic syndrome (MDS) patients with chromosome 4q24 abnormalities. In this cohort ''TET2'' mutations have been observed in 19-26% of patients and are among the most common genetic lesions (Delhommeau et al., 2009; Langemeijer et al., 2009). Cell lineage evidence supports the notion that ''TET2'' mutations occur very early during disease evolution (Itzykson et al., 2013a; Langemeijer et al., 2009). ''TET2'' mutations are overrepresented in samples with normal cytogenetics (Bejar et al., 2011). Mutations in ''EZH2'' occur in as many as 35% of ''TET2''-mutated MDS (Muto et al., 2013). There is no impact of ''TET2'' mutations on overall survival, but their presence may predict response to hypomethylating agents (Bejar et al., 2011; Itzykson et al., 2011).

'''[[Chronic Myelomonocytic Leukemia (CMML)]]'''

'''[[HAEM5:Chronic myelomonocytic leukaemia]]'''

Approximately 60% of chronic myelomonocytic leukemia (CMML) is ''TET2'' mutated (Itzykson et al., 2013b). In CMML ''TET2'' mutations are associated with low-risk cytogenetics and a lower platelet count, typically co-occur with mutations in the splicing gene ''SRSF2'', and are mutually exclusive with ''IDH1'' and ''IDH2'' mutations. ''TET2'' mutation has not previously been found to confer an overall survival advantage (Itzykson et al., 2013b), although a more recent study suggests there is enhanced overall survival in ''TET2''-mutated CMML in the absence of ''ASXL1'' mutations (Patnaik et al., 2016).

Approximately 60% of chronic myelomonocytic leukemia (CMML) is ''TET2'' mutated (Itzykson et al., 2013b). In CMML ''TET2'' mutations are associated with low-risk cytogenetics and a lower platelet count, typically co-occur with mutations in the splicing gene ''SRSF2'', and are mutually exclusive with ''IDH1'' and ''IDH2'' mutations. ''TET2'' mutation has not previously been found to confer an overall survival advantage (Itzykson et al., 2013b), although a more recent study suggests there is enhanced overall survival in ''TET2''-mutated CMML in the absence of ''ASXL1'' mutations (Patnaik et al., 2016).

'''[[Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]]'''

'''[[HAEM4:Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]]'''

In acute myeloid leukemia (AML) ''TET2'' mutations occur in around 28% of patients, of which half have mutations in both alleles (Weissmann et al., 2012). They occur more frequently in patients with normal karyotype and are associated with higher white blood cell counts, lower platelet counts, and a higher age at diagnosis. ''TET2'' mutations predict lower event-free survival, particularly in patients younger than 65 years old and those in the European LeukemiaNet (ELN) favourable-risk subgroup. Overall survival does not seem to be impacted except for in patients with ''TET2'' mutation and intermediate-risk AML, where overall survival is reduced (Patel et al., 2012; Weissmann et al., 2012). There is a strong correlation with ''JAK2'' mutations occurring in patients with ''TET2''-mutated secondary AML after myeloproliferative neoplasm, and there is a highly inverse association between ''TET2'' mutations and mutations in ''IDH1'' and ''IDH2'' (Weissmann et al., 2012). This inverse association is also observed for ''TET2'' and ''WT1'' mutations, and TET2 and WT1 physically interact, suggesting overlapping pathways for these genes in AML (Wang et al., 2015). ''TET2'' mutations increase the response of low blast count AML patients to the hypomethylating agent azacitidine (Itzykson et al., 2011).

In acute myeloid leukemia (AML) ''TET2'' mutations occur in around 28% of patients, of which half have mutations in both alleles (Weissmann et al., 2012). They occur more frequently in patients with normal karyotype and are associated with higher white blood cell counts, lower platelet counts, and a higher age at diagnosis. ''TET2'' mutations predict lower event-free survival, particularly in patients younger than 65 years old and those in the European LeukemiaNet (ELN) favourable-risk subgroup. Overall survival does not seem to be impacted except for in patients with ''TET2'' mutation and intermediate-risk AML, where overall survival is reduced (Patel et al., 2012; Weissmann et al., 2012). There is a strong correlation with ''JAK2'' mutations occurring in patients with ''TET2''-mutated secondary AML after myeloproliferative neoplasm, and there is a highly inverse association between ''TET2'' mutations and mutations in ''IDH1'' and ''IDH2'' (Weissmann et al., 2012). This inverse association is also observed for ''TET2'' and ''WT1'' mutations, and TET2 and WT1 physically interact, suggesting overlapping pathways for these genes in AML (Wang et al., 2015). ''TET2'' mutations increase the response of low blast count AML patients to the hypomethylating agent azacitidine (Itzykson et al., 2011).