Acute promyelocytic leukemia (APL)

01Short answer

02Simple explanation

Normally, myeloid cells mature in the marrow through several stages: myeloblast → promyelocyte → more mature cells → neutrophil. In APL, cells stop at the promyelocyte stage and keep multiplying. These cells are full of tiny grains (granules).

The cause is a swap between two chromosomes: pieces of chromosomes 15 and 17 trade places, and two genes — PML and RARA — fuse. The resulting PML::RARA protein blocks the cell’s “mature now” signal. This change is not inherited — it happens during life in a single cell.

The most dangerous part of APL is the beginning. The granules in promyelocytes disrupt the clotting system: small clots form while clotting factors are used up at the same time. This is called DIC (disseminated intravascular coagulation). It can cause nose and gum bleeding, large bruises and, rarely, bleeding in the brain.

The good news: APL has a very effective, targeted treatment. ATRA (a vitamin A derivative) cancels the effect of the faulty protein and forces the “stuck” cells to mature. Arsenic trioxide breaks down the PML::RARA protein. Together these two drugs give many people the chance of long-lasting remission without chemotherapy.

So when APL is suspected, doctors act urgently: they start ATRA at once, check clotting tests frequently and give platelet and plasma transfusions as needed. Once the first weeks are over, the outlook is very good — APL is considered one of the leukemias with the best results.

03Scientific explanation

APL is defined by the PML::RARA fusion protein; it usually results from t(15;17) but can also arise from cryptic or complex rearrangements. According to the NCI, APL makes up about 5–8% of AML cases and occurs mainly in adults in midlife. Two morphological forms are recognised: typical (hypergranular) and microgranular (hypogranular); in the microgranular form the white count can be very high and rise quickly. Both forms are often accompanied by DIC. The diagnosis is confirmed by FISH, RT-PCR or cytogenetics, but treatment starts without waiting for confirmation.

The risk group is defined by the white cell count at diagnosis: low–intermediate risk means ≤10 × 10⁹/L; high risk means >10 × 10⁹/L. For low–intermediate risk, the standard is ATRA + arsenic trioxide (ATO) without chemotherapy. In a randomized phase III trial in this group, 2-year overall survival was 99% with ATRA + ATO and 91% with ATRA + chemotherapy (NCI PDQ). For high risk, ATRA is combined with an anthracycline (e.g. idarubicin), or with ATO and sometimes gemtuzumab ozogamicin, followed by ATO-based consolidation.

Early deaths are mainly caused by bleeding, differentiation syndrome or infection. Differentiation syndrome is an inflammatory reaction as cells mature rapidly under ATRA or ATO: fever, breathlessness, fluid around the lungs and heart, rapid weight gain (from fluid), swelling, low blood pressure and kidney problems. Recognising it early and treating it with steroids (e.g. dexamethasone) can prevent serious harm. ATO can also prolong the QT interval on the ECG, so electrolytes and ECGs are monitored.

Response is assessed molecularly, by measuring PML::RARA with RT-PCR; the goal by the end of consolidation is molecular remission. Relapse is rare; when it happens, ATO is usually used with or without chemotherapy, and an autologous or allogeneic transplant may then be considered. Targeted treatment of APL is regarded as one of the first successful examples in oncology of a treatment that directly reverses the effect of a genetic abnormality.

04What happens in the body?

One swap — a whole disease

A swap of pieces between chromosomes 15 and 17 joins the PML and RARA genes. The faulty protein that results halts cell maturation at the promyelocyte stage. Every feature of APL — both its danger and its excellent response to treatment — traces back to this single change.

Why is it an emergency?

The granules of promyelocytes disrupt clotting and cause DIC. Because bleeding is the biggest risk in the first days, treatment starts at the stage of suspicion, clotting tests may be checked several times a day, and platelets, plasma or fibrinogen are transfused.

ATRA and arsenic trioxide: treatment that makes cells mature

Unlike ordinary chemotherapy, ATRA does not kill leukemia cells directly — it forces them to mature like normal cells, after which they die naturally. Arsenic trioxide breaks down the faulty protein. This combination is the standard treatment for low–intermediate risk.

Differentiation syndrome: what to watch for

If fever, breathlessness, rapid weight gain or swelling appear in the first weeks of treatment, tell your medical team straight away. This may be differentiation syndrome, which is treated quickly with steroids. Your team will watch you closely during this period.

07Key terms

APL

Acute promyelocytic leukemia — a type of AML defined by PML::RARA.

Promyelocyte

The granule-filled maturation stage after the myeloblast.

PML::RARA

A fusion gene formed by joining genes from chromosomes 15 and 17.

Translocation

A swap of pieces between two chromosomes.

DIC

Disseminated intravascular coagulation — a clotting disorder causing both clots and bleeding.

ATRA

All-trans retinoic acid — a vitamin A derivative that makes cells mature.

Arsenic trioxide (ATO)

A drug that breaks down the PML::RARA protein.

Differentiation syndrome

An inflammatory reaction during rapid maturation of cells.

Fibrinogen

A blood protein needed to form a clot.

Molecular remission

PML::RARA can no longer be detected by a sensitive test.

08Key points

• APL is a special type of AML defined by the PML::RARA fusion gene.
• Cells get stuck at the promyelocyte stage.
• The main early danger is a clotting disorder (DIC) and bleeding.
• ATRA starts immediately on suspicion — confirmation is not awaited.
• For low–intermediate risk, ATRA + arsenic trioxide is highly effective without chemotherapy.
• Report signs of differentiation syndrome to your team straight away.
• After the first weeks, the outlook is very good; relapse is rare.

09Frequently asked questions

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

1. 1

   Has APL treatment already been started?

2. 2

   What is being done now to reduce the risk of bleeding?

3. 3

   Which signs of differentiation syndrome should I watch for?

4. 4

   How will PCR monitoring be done after treatment ends?

My questions

11What to read next

• Understanding leukemiaAcute myeloid leukemia (AML)
• Understanding leukemiaChromosomes
• Understanding leukemiaWhy do symptoms occur?
• Understanding leukemiaAcute lymphoblastic leukemia (ALL)
• Treatment and the treatment processTargeted therapy

12Sources

1. National Cancer Institute (NCI). Adult Acute Myeloid Leukemia Treatment (PDQ®) — Health Professional Version: Treatment of APL
2. National Cancer Institute (NCI). Adult Acute Myeloid Leukemia Treatment (PDQ®) — Patient Version
3. American Cancer Society. Treatment of Acute Promyelocytic Leukemia (APL)
4. American Cancer Society. Non-Chemo Drugs for Acute Promyelocytic Leukemia (APL)
5. American Cancer Society. How Is Acute Myeloid Leukemia Classified?
6. Cleveland Clinic. Differentiation Syndrome: Symptoms, Causes & Treatment
7. MedlinePlus (U.S. National Library of Medicine). Disseminated intravascular coagulation (DIC)
8. National Human Genome Research Institute. Translocation
9. Blood (American Society of Hematology), 2022. Diagnosis and management of AML in adults: 2022 ELN recommendations
10. Leukemia (Nature) — WHO 5th edition. WHO Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
11. NHS. Acute myeloid leukaemia