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Gene Symbol TET2
Synonyms IMD75 | KIAA1546 | MDS
Gene Description TET2, methylcytosine dioxygenase TET2, is a member of the ten-eleven-translocation family of genes that plays a role in DNA methylation and is involved in hematopoesis (PMID: 26099018, PMID: 25510268, PMID: 27848178). TET2 has been identified as a tumor suppressor in hematological malignancies, and mutations in TET2 are common in hematological cancers including myelodysplastic syndrome, chronic myelomoncytic leukemia, and atypical CML (PMID: 26099018, PMID: 22240200, PMID: 30138727) and epigenetic dysregulation has been observed in glioblastoma (PMID: 29899831).
NCBI Gene ID Chromosome Map Location Canonical Transcript Gene Role
54790 4 4q24 NM_001127208 Tumor suppressor (PMID: 30606230)

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
TET2 A1505T TET2 mut acute myeloid leukemia sensitive Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment inhibited colony formation of patient-derived acute myeloid leukemia cells harboring FLT3-ITD and a TET2 mutation along with an NPM1 mutation and expressing TET2 A1505T in culture (PMID: 34215619). 34215619
TET2 mutant acute myeloid leukemia predicted - sensitive Azacitidine Phase I Actionable In a retrospective analysis, presence of a TET2 mutation correlated with higher overall response rate (ORR) in patients with myelodysplastic syndrome and acute myeloid leukemia following treatment with Vidaza (azacitidine), with an ORR of 85% (11/3) in TET2-mutated patients, compared to 47% (34/47) in patients with wild-type TET2, but did not correlate with overall survival (PMID: 21494260). 21494260
TET2 mutant acute myeloid leukemia sensitive Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment inhibited colony formation in patient-derived acute myeloid leukemia cells harboring a TET2 mutation along with FLT3-ITD and NPM1 mutation in culture (PMID: 34215619). 34215619
TET2 mutant myelofibrosis not applicable N/A Guideline Diagnostic TET2 mutations aid in the diagnosis of primary myelofibrosis in the absence of JAK2, CALR, or MPL mutations (NCCN.org). detail...
TET2 mutant acute myeloid leukemia not applicable N/A Clinical Study Prognostic In multiple clinical studies, including a meta-analysis, TET2 mutations were associated with shorter overall survival in patients with acute myeloid leukemia (PMID: 24524305, PMID: 25412851, PMID: 24994606). 24524305 25412851 24994606
TET2 mutant angioimmunoblastic T-cell lymphoma not applicable N/A Guideline Diagnostic TET2 mutations aid in the diagnosis of angioimmunoblastic T-cell lymphoma (NCCN.org). detail...
DNMT3A mut TET2 mut acute myeloid leukemia sensitive Olaparib Preclinical - Patient cell culture Actionable In a preclinical study, Lynparza (olaparib) treatment inhibited colony formation in patient-derived acute myeloid leukemia cells co-harboring a DNMT3A and TET2 mutation along with FLT3-ITD and NPM1 mutation in culture (PMID: 34215619). 34215619
FLT3 exon 14 ins TET2 mut acute myeloid leukemia sensitive Olaparib + Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib) and Vanflyta (quizartinib) inhibited colony formation in patient-derived acute myeloid leukemia cells harboring FLT3-ITD and a TET2 mutation along with an NPM1 mutation in culture (PMID: 34215619). 34215619
FLT3 exon 14 ins TET2 mut acute myeloid leukemia sensitive Doxorubicin + Olaparib + Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib), Adriamycin (doxorubicin), and Vanflyta (quizartinib) inhibited colony formation in patient-derived acute myeloid leukemia cells harboring FLT3-ITD and a TET2 mutation along with an NPM1 mutation in culture (PMID: 34215619). 34215619
DNMT3A mut FLT3 exon 14 ins TET2 mut acute myeloid leukemia sensitive Olaparib + Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib) and Vanflyta (quizartinib) inhibited colony formation in patient-derived acute myeloid leukemia cells harboring FLT3-ITD and DNMT3A and TET2 mutations along with an NPM1 mutation in culture (PMID: 34215619). 34215619
DNMT3A mut FLT3 exon 14 ins TET2 mut acute myeloid leukemia sensitive Doxorubicin + Olaparib + Quizartinib Preclinical - Patient cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib), Adriamycin (doxorubicin), and Vanflyta (quizartinib) inhibited colony formation in patient-derived acute myeloid leukemia cells harboring FLT3-ITD and DNMT3A and TET2 mutations along with an NPM1 mutation in culture (PMID: 34215619). 34215619
TET2 loss acute myeloid leukemia sensitive Talazoparib Preclinical - Cell culture Actionable In a preclinical study, Talzenna (talazoparib) decreased colony formation in mouse acute myeloid leukemia cells harboring TET2 loss along with a FLT3-ITD mutation in culture (PMID: 34215619). 34215619
TET2 loss acute myeloid leukemia sensitive Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) inhibited colony formation in mouse acute myeloid leukemia cells harboring TET2 loss along with various oncogenic tyrosine kinase mutations in culture (PMID: 34215619). 34215619
TET2 loss leukemia sensitive TETi76 Preclinical - Cell line xenograft Actionable In a preclinical study, TETi76 treatment reduced viability and colony formation of a TET2-null leukemia cell line in culture, decreased viability of bone marrow derived mononuclear cells from TET2-null mouse model, and reduced tumor burden in a TET2-null subcutaneous xenograft model (PMID: 33681816). 33681816
DNMT3A loss TET2 loss acute myeloid leukemia sensitive Talazoparib Preclinical - Cell culture Actionable In a preclinical study, Talzenna (talazoparib) decreased colony formation in murine acute myeloid leukemia cells harboring TET2 and DNMT3A loss along with a FLT3-ITD mutation in culture (PMID: 34215619). 34215619
DNMT3A loss TET2 loss acute myeloid leukemia sensitive Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) inhibited colony formation in murine acute myeloid leukemia cells harboring TET2 and DNMT3A loss along wtih various oncogenic tyrosine kinase mutations in culture (PMID: 34215619). 34215619
FLT3 exon 14 ins TET2 loss acute myeloid leukemia sensitive Olaparib + Quizartinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib) and Vanflyta (quizartinib) decreased colony formation in murine acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 loss in culture (PMID: 34215619). 34215619
FLT3 exon 14 ins TET2 loss acute myeloid leukemia sensitive Doxorubicin + Olaparib + Quizartinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib), Adriamycin (doxorubicin), and Vanflyta (quizartinib) increased DNA double-strand breaks and decreased colony formation in mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 loss in culture (PMID: 34215619). 34215619
FLT3 exon 14 ins TET2 loss acute myeloid leukemia sensitive Quizartinib + Talazoparib Preclinical - Cell culture Actionable In a preclinical study, the combination of Vanflyta (quizartinib) and Talzenna (talazoparib) decreased colony formation in mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 loss in culture (PMID: 34215619). 34215619
DNMT3A loss FLT3 exon 14 ins TET2 loss acute myeloid leukemia sensitive Olaparib + Quizartinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib) and Vanflyta (quizartinib) decreased colony formation in mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 and DNMT3A loss in culture (PMID: 34215619). 34215619
DNMT3A loss FLT3 exon 14 ins TET2 loss acute myeloid leukemia sensitive Doxorubicin + Olaparib + Quizartinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Lynparza (olaparib), Adriamycin (doxorubicin), and Vanflyta (quizartinib) increased DNA double-strand breaks and decreased colony formation in mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 and DNMT3A loss in culture (PMID: 34215619). 34215619
DNMT3A loss FLT3 exon 14 ins TET2 loss acute myeloid leukemia sensitive Quizartinib + Talazoparib Preclinical - Cell culture Actionable In a preclinical study, the combination of Vanflyta (quizartinib) and Talzenna (talazoparib) decreased colony formation in mouse acute myeloid leukemia cells harboring a FLT3-ITD mutation and TET2 and DNMT3A loss in culture (PMID: 34215619). 34215619
JAK2 V617F TET2 loss acute myeloid leukemia sensitive Olaparib + Rituximab Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Lynparza (olaparib) and Rituxan (rituximab) decreased colony formation in mouse acute myeloid leukemia cells harboring JAK2 V617F and TET2 loss in culture (PMID: 34215619). 34215619
JAK2 V617F TET2 loss acute myeloid leukemia sensitive Hydroxyurea + Olaparib + Rituximab Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib), Droxia (hydroxyurea), and Rituxan (rituximab) combination treatment decreased colony formation in mouse acute myeloid leukemia cells harboring JAK2 V617F and TET2 loss in culture (PMID: 34215619). 34215619
TET2 T1063Nfs*5 TET2 E1207K angioimmunoblastic T-cell lymphoma predicted - sensitive Dasatinib Case Reports/Case Series Actionable In a Phase I trial, four patients with relapsed/refractory angioimmunoblastic T-cell lymphoma harboring TET2 mutations and/or RHOA G17V achieved a partial response within 30 days of Sprycel (dasatinib) treatment, including one patient harboring TET2 T1063Nfs*5 and TET2 E1207K who maintained the partial response at the time of trial discontinuation (PMID: 32107212). 32107212
BRAF V600E TET2 V1199E high grade glioma resistant Vemurafenib Preclinical - Cell culture Actionable In a preclinical study, a glioma cell line harboring BRAF V600E developed resistance after prolonged exposure to Zelboraf (vemurafenib) in culture, and was subsequently found to have acquired TET2 V1199E (PMID: 34433654). 34433654
TET2 del acute myeloid leukemia sensitive Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) inhibited colony formation of mouse acute myeloid leukemia cells harboring TET2 deletion along with a FLT3-ITD mutation in culture (PMID: 34215619). 34215619
TET2 del acute myeloid leukemia sensitive Selinexor Preclinical - Cell culture Actionable In a preclinical study, Xpovio (selinexor) induced apoptosis in TET2-knockout acute myeloid leukemia cell lines, resulting in decreased cell viability in culture (PMID: 36746437). 36746437
TET2 del acute myeloid leukemia sensitive Eltanexor Preclinical - Cell culture Actionable In a preclinical study, Eltanexor (KPT-8602) induced apoptosis in TET2-knockout acute myeloid leukemia cell lines, resulting in decreased cell viability in culture (PMID: 36746437). 36746437
DNMT3A del TET2 del acute myeloid leukemia sensitive Olaparib Preclinical - Cell culture Actionable In a preclinical study, Lynparza (olaparib) inhibited colony formation of mouse acute myeloid leukemia cells harboring TET2 and DNMT3A deletion along with a FLT3-ITD mutation in culture (PMID: 34215619). 34215619