{"entity":{"id":"apl","kind":"cancer","name":"Acute promyelocytic leukaemia","aka":["APL","AML-M3","PML::RARA acute leukaemia","Promyelocytic leukaemia"],"tldr":"Acute promyelocytic leukaemia is caused by a single fused gene that freezes blood cells at an immature stage and triggers dangerous bleeding. Two non-chemotherapy drugs, a vitamin A derivative and arsenic trioxide, make the cells mature and cure more than nine in ten patients.","summary":"The t(15;17) translocation fuses PML to the retinoic acid receptor alpha gene. The PML::RARA protein blocks differentiation at the promyelocyte stage, and the promyelocytes release procoagulants that cause a bleeding and clotting disorder responsible for most early deaths. Diagnosis is a clinical emergency: all-trans retinoic acid (ATRA) is started on suspicion, before the fusion is confirmed, together with aggressive platelet and fibrinogen replacement. Risk is set by the white count at presentation, above 10 x 10^9/L being high risk.\n\nATRA, introduced in Shanghai in 1988, was the first differentiation therapy for any cancer; with anthracycline chemotherapy it lifted cure rates above 70 percent. Arsenic trioxide, developed in Harbin and Shanghai in the 1990s and approved in the United States for relapsed disease in 2000, degrades the fusion protein itself. The Italian-German APL0406 trial, reported in 2013, randomised low- and intermediate-risk patients to ATRA plus arsenic or ATRA plus chemotherapy: two-year event-free survival 97 percent versus 86 percent, with fewer infections and no secondary leukaemias, and the chemotherapy-free regimen became the standard, approved for first-line use in Europe in 2016 and the United States in 2018. High-risk patients receive ATRA and arsenic with an anthracycline or gemtuzumab ozogamicin added for the first weeks.\n\nDifferentiation syndrome, fever, fluid retention and lung infiltrates as the cells mature, affects around a quarter of patients and is treated with dexamethasone; QT prolongation and liver toxicity are watched on arsenic. Molecular monitoring for PML::RARA after consolidation catches the rare relapse, which is treated with arsenic-based regimens and autologous transplant. The remaining deaths are early haemorrhagic deaths before treatment starts, so the research target is recognition and access rather than a new drug.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Acute_promyelocytic_leukemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Acute_promyelocytic_leukemia"},{"label":"NCCN Guidelines: Acute Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411"}],"tags":["subtype-page"],"related":[],"cancers":[],"sections":[],"technologies":["cytogenetics-fish","transfusion-support"],"targets":["rara"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["differentiation-syndrome","mrd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"About one in ten cases of acute myeloid leukaemia; once the most rapidly fatal, it is now the most curable, with more than nine in ten patients cured when early bleeding is prevented.","subtypes":["Low- and intermediate-risk APL (white count 10 x 10^9/L or below)","High-risk APL (white count above 10 x 10^9/L)","Variant APL with RARA fusions other than PML (ZBTB16, NPM1, STAT5B; some resist arsenic or ATRA)","Therapy-related APL"],"biomarkers":["PML::RARA fusion by PCR or FISH","t(15;17) karyotype","White cell count at presentation (Sanz risk)","Fibrinogen, D-dimer and platelet count","PML::RARA transcript MRD after consolidation","FLT3-ITD (common in the microgranular variant)"],"standardOfCare":[{"setting":"Suspected APL, first hours","approach":"Start all-trans retinoic acid on morphological suspicion; transfuse platelets and fibrinogen to targets; avoid invasive procedures until coagulopathy is controlled.","refs":["tretinoin-atra","transfusion-support"],"guideline":{"version":"NCCN Guidelines: Acute Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411"}},{"setting":"Low- and intermediate-risk","approach":"All-trans retinoic acid plus arsenic trioxide induction and consolidation without chemotherapy (APL0406); dexamethasone prophylaxis or treatment for differentiation syndrome.","refs":["tretinoin-atra","arsenic-trioxide","dexamethasone"],"guideline":{"version":"NCCN Guidelines: Acute Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411"}},{"setting":"High-risk","approach":"All-trans retinoic acid plus arsenic trioxide with idarubicin or gemtuzumab ozogamicin added during induction to control the white count.","refs":["tretinoin-atra","arsenic-trioxide","idarubicin","gemtuzumab-ozogamicin"],"guideline":{"version":"NCCN Guidelines: Acute Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411"}},{"setting":"Molecular relapse","approach":"Arsenic-based salvage to molecular remission, then autologous transplant if PML::RARA negative, allogeneic transplant if not.","refs":["arsenic-trioxide","autologous-stem-cell-transplant","allogeneic-hsct"],"guideline":{"version":"NCCN Guidelines: Acute Myeloid Leukemia","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1411"}}],"stateOfArt":["A chemotherapy-free regimen of all-trans retinoic acid and arsenic trioxide cures more than nine in ten patients with standard-risk disease.","Early death from bleeding, before or during the first days of treatment, is now the main cause of failure.","Oral arsenic formulations are replacing intravenous arsenic in China and in trials elsewhere."],"history":[{"year":1957,"title":"Hillestad describes acute promyelocytic leukaemia","refs":[]},{"year":1977,"title":"t(15;17) translocation identified","refs":["cytogenetics"]},{"year":1988,"title":"All-trans retinoic acid produces remissions in Shanghai: the first differentiation therapy","refs":["tretinoin-atra"]},{"year":2000,"title":"Arsenic trioxide approved for relapsed APL","refs":["arsenic-trioxide"]},{"year":2013,"title":"APL0406: retinoic acid plus arsenic beats retinoic acid plus chemotherapy","refs":["tretinoin-atra","arsenic-trioxide"]},{"year":2018,"title":"Arsenic trioxide approved for first-line standard-risk APL in the United States","refs":["arsenic-trioxide"]}],"pipeline":["arsenic-trioxide","tretinoin-atra"],"openProblems":["Early haemorrhagic death before treatment starts, especially where diagnosis is slow.","Treatment of variant RARA fusions that do not respond to arsenic or retinoic acid.","Whether high-risk patients can also be spared chemotherapy."],"parent":"aml"},"route":"/cancers/apl/","neighbours":{"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"},{"id":"transfusion-support","kind":"technology","name":"Transfusion support and anaemia management","route":"/technologies/transfusion-support/"}],"target":[{"id":"rara","kind":"target","name":"Retinoic acid receptor alpha (RARA)","route":"/targets/rara/"}],"term":[{"id":"cytogenetics","kind":"term","name":"Cytogenetics and karyotype","route":"/terms/cytogenetics/"},{"id":"differentiation-syndrome","kind":"term","name":"Differentiation syndrome","route":"/terms/differentiation-syndrome/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"}],"drug":[{"id":"arsenic-trioxide","kind":"drug","name":"Arsenic trioxide","route":"/drugs/arsenic-trioxide/"},{"id":"dexamethasone","kind":"drug","name":"Dexamethasone","route":"/drugs/dexamethasone/"},{"id":"gemtuzumab-ozogamicin","kind":"drug","name":"Gemtuzumab ozogamicin","route":"/drugs/gemtuzumab-ozogamicin/"},{"id":"idarubicin","kind":"drug","name":"Idarubicin","route":"/drugs/idarubicin/"},{"id":"tretinoin-atra","kind":"drug","name":"Tretinoin (all-trans retinoic acid, ATRA)","route":"/drugs/tretinoin-atra/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"aml-paediatric","kind":"cancer","name":"Acute myeloid leukaemia in children","route":"/cancers/aml-paediatric/"}]}}