PML-RARA
- Also Known As:
- PML-RARA t(15;17)(q22;q12)
- Acute Promyelocytic Leukemia
- AML-M3
- Formal Name:
- Promyelocytic Leukemia/Retinoic Acid Receptor Alpha

This page was fact checked by our expert Medical Review Board for accuracy and objectivity. Read more about our editorial policy and review process.
At a Glance
Why Get Tested?
To help diagnose acute promyelocytic leukemia (APL), a type of acute myeloid leukemia (AML); to help guide and/or monitor treatment of APL or to monitor for leukemia cells that remain after treatment (minimal residual disease) or for disease recurrence
When To Get Tested?
When you have results of a complete blood count (CBC) and/or signs and symptoms that suggest that you may have leukemia; periodically when you are being treated for APL and/or when you are in remission but need follow up
Sample Required?
A blood sample drawn from a vein in your arm or a bone marrow sample collected using a bone marrow aspiration procedure
Test Preparation Needed?
None
What is being tested?
Promyelocytic leukemia/retinoic acid receptor alpha or PML-RARA refers to an abnormal fusion gene sequence. It is a specific rearrangement of genetic material from two separate chromosomes (chromosomal translocation) and is associated with a specific type of leukemia. This test detects and measures PML-RARA in the blood or bone marrow to determine if an individual has acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML).
Humans normally have 23 pairs of chromosomes, including 22 pairs of non-sex-determining chromosomes (also known as autosomes) and 1 pair of sex chromosomes (XX for females, XY for males). The genetic makeup of a person is contained on her/his chromosomes. The genes that reside on chromosomes form the blueprints for the production of thousands of proteins. Sometimes changes can occur to a person’s chromosomes and/or genes during their lifetime because of exposures to radiation, toxins, or for unknown reasons. These exposures could lead to gene mutations or to chromosome translocations.
The PML-RARA fusion gene sequence is one such acquired change (mutation) that is formed when pieces of chromosome 15 and chromosome 17 break off and switch places (translocate). The PML gene region in chromosome 15 then fuses with the RARA gene region in chromosome 17. This is referred to as reciprocal translocation, and this particular one is commonly expressed as t(15;17).
Normally, the PML gene codes for a protein that helps prevent uncontrolled cell growth and acts as a tumor suppressor. The RARA gene codes for a protein that is crucial for white blood cell (WBC) maturation, as these cells typically develop through several stages in the bone marrow before release into circulation. The mutated PML-RARA fusion gene codes for an abnormal fusion protein that does neither of these functions but instead leads to the uncontrolled production and accumulation of leukemic WBCs that do not mature or differentiate beyond the promyelocyte stage. As a large number of these abnormal cells start to crowd out the normal blood cell precursors in the bone marrow, signs and symptoms of leukemia start to emerge.
Up to 98% of cases of acute promyelocytic leukemia have a characteristic t(15;17) PML-RARA reciprocal chromosomal translocation. In about 2% of APL cases, other translocations involving the RARA gene and genes other than PML have been reported.
Testing detects the PML-RARA fusion gene or its transcripts, the RNA copies made by the cell from the abnormal gene sequence of DNA. The presence of the PML-RARA abnormality helps confirm the diagnosis of APL.
Testing can also direct APL therapy and monitor minimal residual disease, which could be fatal. Treatment of APL typically involves all-trans retinoic acid (ATRA), a drug that binds to retinoic acid receptors in cells. The drug can overcome the effect of the abnormal PML-RARA protein and induce downstream signaling and maturation of WBCs. This therapy works well in conjunction with chemotherapy but only in those cases where the PML-RARA fusion gene is present. The treatment results in remission in about 80-90% of these patients, according to the American Cancer Society. A small percentage of people with APL have a fusion between the RARA gene and a different gene, and they may or may not benefit from ATRA therapy based upon the specific gene involved.
Common Questions
Related Content
On This Site
Tests: Complete Blood Count; Bone Marrow Aspiration and Biopsy; Blood Smear; WBC Differential
Elsewhere On The Web
American Society of Hematology: Leukemia
American Cancer Society: Acute Myeloid Leukemia (AML)
Genetics Home Reference: Acute promyelocytic leukemia
National Cancer Institute: Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version
MedlinePlus Health Information: Acute Myeloid Leukemia
Leukemia & Lymphoma Society: Acute Myeloid Leukemia
View Sources
Sources Used in Current Review
2017 review performed by Omar Ramadan, PhD, MSc, MT (ASCPi) and the Testing.com Editorial Review Board.
Hudnall, S. David. Hematology: A Pathophysiologic Approach. Mosby, 2012. The Mosby Physiology Monograph Series. EBSCOhost. Pg 88. Accessed on 03/19/[email protected]:56 through Sentara Knowledge Online Resources (SKOR).
De Angelis F, Breccia M. Molecular Monitoring as a Path to Cure Acute Promyelocytic Leukemia. Rare Cancers Ther (2015) 3:119–132.
Lo-Coco F, Hasan SK. Understanding the molecular pathogenesis of acute promyelocytic leukemia. Best Pract Res Clin Haematol. 2014 Mar;27(1):3-9.
Bullinger L, Döhner 1, Döhner H. Genomics of Acute Myeloid Leukemia Diagnosis and Pathways. J Clin Oncol. 2017 Mar 20;35(9):934-946.
Grimwade D, Jovanovic JV, Hills RK. Can we say farewell to monitoring minimal residual disease in acute promyelocytic leukaemia? Best Pract Res Clin Haematol. 2014 Mar;27(1):53-61.
Chendamarai E, Balasubramanian P, George B, et al. Role of minimal residual disease monitoring in acute promyelocytic leukemia treated with arsenic trioxide in frontline therapy. Blood. 2012 Apr 12;119(15):3413-9.
Levine K, DeBlasio A, Miller WH Jr. Molecular diagnosis and monitoring of acute promyelocytic leukemia treated with retinoic acid. Leukemia. 1994 Apr;8 Suppl 1:S116-20.
Lengfelder E, Lo-Coco F, Ades L, et al. Arsenic trioxide-based therapy of relapsed acute promyelocytic leukemia: registry results from the European LeukemiaNet. Leukemia. 2015 May;29(5):1084-91.
Burnett AK, Hills RK, Grimwade D, et al. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial.
Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21.
Jovanovic JV, Rennie K, Culligan D, et al. Development of real-time quantitative polymerase chain reaction assays to track treatment response in retinoid resistant acute promyelocytic leukemia. Front Oncol. 2011 Oct 25;1:35.
Sources Used in Previous Reviews
Seiter, K. (Updated 2012 March 9). Acute Myelogenous Leukemia. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/197802-overview#showall. Accessed May 2013.
Yang, J. and Schiffer, C. (2012). Genetic Biomarkers in Acute Myeloid Leukemia. Medscape Today News from Expert Rev Hematol. 2012;5(4):395-407. [On-line information]. Available online at http://www.medscape.com/viewarticle/771810. Accessed May 2013.
Mason, J. and Griffiths, M. (2012). Molecular Diagnosis of Leukemia. Medscape Today News from Expert Rev Mol Diagn. 2012;12(5):511-526. [On-line information]. Available online at http://www.medscape.com/viewarticle/766770. Accessed May 2013.
Kelley, T. and South, S. (2013 March). Acute Myeloid Leukemia – AML. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/AML.html?client_ID=LTD. Accessed May 2013.
(© 1995–2013). PML/RARA Quantitative, PCR. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-info/hematology/catalog/Overview/84114. Accessed May 2013.
(Reviewed 2011 April). Acute promyelocytic leukemia. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/condition/acute-promyelocytic-leukemia. Accessed April 2013.
(Reviewed 2011 April). RARA. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/gene/RARA. Accessed April 2013.
Kelley, T. and Schumacher, J. (2012 August). PML-RARA , t(15;17) Quantitation by RT-PCR ARUP. ARUP Laboratories [On-line information]. PDF available for download at http://www.aruplab.com/Testing-Information/resources/TechnicalBulletins/PML-RARAt%2815;17%29QuantitationbyRT-PCR.pdf. Accessed April 2013.
VanderWalde, A. and Vora, N. (2012 June 18). Genetics of Acute Myeloid Leukemia Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1936033-overview. Accessed April 2013.
Kotiah, S. and Besa, E. (Updated 2011 August 2). Acute Promyelocytic Leukemia Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1495306-overview#showall. Accessed April 2013.
Polampalli, S., et. al. (2011) Role of RT-PCR and FISH in diagnosis and monitoring of acute promyelocytic leukemia. Indian J Cancer v 48:60-7. Available online through http://www.indianjcancer.com. Accessed May 2013.
Nasr, R. Et. al. (2009) Therapy-induced PML/RARA Proteolysis and Acute Promyelocytic Leukemia Cure. Clin Cancer Res v 15:6321-6326. [On-line information]. Available online at http://clincancerres.aacrjournals.org/content/15/20/6321.full. Accessed April 2013.
Ommen, H. et. al. (2010 January 14). Strikingly different molecular relapse kinetics in NPM1c, PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 acute myeloid leukemias. Blood v 115 (2) 198-205 [On-line information]. Available online at http://bloodjournal.hematologylibrary.org/content/115/2/198.full. Accessed April 2013.
(Reviewed 2011 December). PML/RARA t(15;17) Translocation, FISH and Quantitative Real-Time PCR. Quest Diagnostics [On-line information]. Available online at http://www.questdiagnostics.com/testcenter/testguide.action?dc=TH_PML_RARA. Accessed May 2013.
Ask a Laboratory Scientist
