• What is PML-RARA?
  • PML-RARA in Acute Myeloid Leukemia
  • PML-RARA Fusion
  • Clinical Trials

PML-RARA

Promyelocytic leukemia (PML), is a gene that encodes for a transcription factor and tumor suppressor protein (Gene 2013a). PML is involved in rearrangements observed in AML, particularly APL (acute promyelocytic leukemia).

Retinoic acid receptor, alpha (RARA) is a gene that encodes for a nuclear retinoic acid receptor, a transcription regulating protein (Gene 2013b). In cancer, rearrangements involving RARA have been observed in AML and APL. Its role is also being investigated in gastric and other cancers.

The PML-RARA fusion has been observed in most cases of APL.

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

Suggested Citation: Seegmiller, A., M. Jagasia. 2013. PML-RARA. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/pml-rara/?tab=0 (Updated June 4).

Last Updated: June 4, 2013

PML-RARA Fusion Gene in Acute Myeloid Leukemia

The PML-RARA fusion gene, t(15;17)(q24.1;21.1), is the primary cytogenetic abnormality leading to acute promyelocytic leukemia, a sub-type of AML. PML-RARA fusion proteins exhibit altered transcription factor behavior compared to wild type PML and RARA. Additional mutations may be required for leukemogenesis (Reiter, Lengfelder, and Grimwade 2004).​ PML-RARA 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. PML-RARA Fusion Gene in Acute Myeloid Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/pml-rara/ (Updated September 9).

Last Updated: September 9, 2013

PML-RARA t(15;17)(q22;q12) Translocation in Acute Myeloid Leukemia

Properties
Location of translocation Chromosomal rearrangements involving the PML gene on 15q22 and the RARA gene on 17q12
Frequency of PML-RARA translocation in AML 13% (Grimwade et al. 2010; Zhang and Le Beau 2013)
Implications for Targeted Therapeutics
Response to FLT3 inhibitors Currently no role for PML-RARA in predicting response
Response to MEK inhibitors Currently no role for PML-RARA in predicting response
Response to JAK2 inhibitors Currently no role for PML-RARA in predicting response
Response to DOT1L inhibitors Currently no role for PML-RARA​ in predicting response
Response to all-trans-retinoic acid and arsenic trioxide Confers sensitivitya

The PML-RARA gene fusion created by the t(15;17)(q22;q12) translocation is associated with favorable prognosis in AML. Most cases of a subtype of AML, acute promyelocytic leukemia, possess a PML-RARA translocation.

a Complete response rates using one or both of these drugs exceed 90% (Iland and Seymour 2013). The NCCN recommends use of ATRA during treatment induction for APL and ATO as a treatment option in consolidation therapy (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. PML-RARA t(15;17)(q22;q12) Translocation in Acute Myeloid Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/pml-rara/253/ (Updated June 15).

Last Updated: June 15, 2015

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