• What is RUNX1-RUNX1T1?
  • RUNX1-RUNX1T1 in Acute Myeloid Leukemia
  • RUNX1-RUNX1T1 Fusion
  • Clinical Trials

RUNX1-RUNX1T1

Runt-related transcription factor 1 (RUNX1; also known as AML1) is a gene that codes for the alpha subunit of the core binding factor protein. This protein is thought to take part in regulating expression of multiple genes involved in normal hematopoiesis (Gene 2013; Kurokawa and Hirai 2003). RUNX1 is involved in translocations observed in hematologic malignancies, including AML, ALL, and myelodysplastic syndromes. Its role in cancer is also being investigated in promyelocytic leukemia, as well as in solid tumors such as endometrial, ovarian, and breast cancer. In addition, germline RUNX1 mutations, deletions, and translocations have been associated with conditions that predispose individuals to myeloid malignancies (Cazzola, Della Porta, and Malcovati 2013; Michaud et al. 2002; NCCN 2014; Song et al. 1999).

Runt-related transcription factor 1; translocated to, 1 (cyclin D-related), also known as RUNX1T1, is a gene that codes for a transcription-regulating protein (UniProt 2013). Other synonyms for RUNX1T1 include AML1T1, ETO, and MTG8. RUNX1T1’s role in AML is well documented. RUNX1T1 may also play a role in CML and other leukemias, as well as pancreatic and ovarian cancers.

The RUNX1-RUNX1T1 fusion has been primarily observed in acute myeloid leukemia.

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Contributors: Adam Seegmiller, M.D., Ph.D., Madan Jagasia, M.B.B.S., M.S.

Suggested Citation: Seegmiller, A., M. Jagasia. 2014. RUNX1-RUNX1T1. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/runx1-runx1t1/?tab=0 (Updated September 10).

Last Updated: September 10, 2014

RUNX1-RUNX1T1 Fusion Gene in Acute Myeloid Leukemia

The RUNX1-RUNX1T1 fusion gene, t(8;21)(q22;q22), is seen in about 5-12% of all AML (Grimwade et al. 2010; Lam and Zhang 2012; Zhang and Le Beau 2013). Research has shown that while RUNX1-RUNX1T1 fusion proteins cause changes to hematopoiesis, they are unlikely to cause AML on their own. Instead, the RUNX1-RUNX1T1 fusion gene may require a “second hit,” an additional mutation or mutations, to cause AML (Lam and Zhang 2012).​ RUNX1-RUNX1T1 fusion genes fall into class II of the “two-hit” theory of leukemogenesis (Naoe and Kiyoi 2013).

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Contributors: Adam Seegmiller, M.D., Ph.D., Madan Jagasia, M.B.B.S., M.S., Scott Wheeler, Ph.D. (through June 2014), Cindy L. Vnencak-Jones, Ph.D.

Suggested Citation: Seegmiller, A., M. Jagasia, S. Wheeler, C. Vnencak-Jones. 2013. RUNX1-RUNX1T1 Fusion Gene in Acute Myeloid Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/runx1-runx1t1/ (Updated September 9).

Last Updated: September 9, 2013

RUNX1-RUNX1T1 t(8;21)(q22;q22) Translocation in Acute Myeloid Leukemia

Properties
Location of translocation Chromosomal rearrangements involving the RUNX1 gene on 21q22 and the RUNX1T1 gene on 8q22
Frequency of RUNX1-RUNX1T1 translocation in AML ~5-12% of all AML (Grimwade et al. 2010; Lam and Zhang 2012; Zhang and Le Beau 2013)
Implications for Targeted Therapeutics
Response to FLT3 inhibitors Currently no role for RUNX1-RUNX1T1 in predicting response
Response to MEK inhibitors Currently no role for RUNX1-RUNX1T1 in predicting response
Response to JAK2 inhibitors Currently no role for RUNX1-RUNX1T1 in predicting response
Response to DOT1L inhibitors Currently no role for RUNX1-RUNX1T1 in predicting response

The RUNX1-RUNX1T1 gene fusion created by the t(8;21)(q22;q22) translocation is associated with favorable prognosis in AML (De Lima et al. 1997; Estey 2012).

In addition, the RUNX1-RUNX1T1 gene fusion is associated with intermediate prognosis when it occurs in combination with a KIT mutation (NCCN 2012).

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Contributors: Adam Seegmiller, M.D., Ph.D., Madan Jagasia, M.B.B.S., M.S.

Suggested Citation: Seegmiller, A., M. Jagasia. 2015. RUNX1-RUNX1T1 t(8;21)(q22;q22) Translocation in Acute Myeloid Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/runx1-runx1t1/251/ (Updated October 16).

Last Updated: October 16, 2015

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