Acute promyelocytic leukemia
Other Names: Acute myeloblastic leukemia type 3; Acute myeloid leukemia with t(15;17)(q22;q12);(PML/RARalpha) and variants; AML M3
Acute promyelocytic leukemia (APL) is an aggressive type of acute myeloid leukemia in which there are too many immature blood-forming cells (promyelocytes) in the blood and bone marrow.This build up of promyelocytes leads to a shortage of normal white and red blood cells and platelets in the body.
signs and symptoms
The signs and symptoms of APL include an increased risk to both bleed and form blood clots. Individuals may also experience excessive tiredness, pain in affected areas, loss of appetite, and weight loss. some symptoms are listed below.
30%-79% of people have these symptoms
- Low number of red blood cells or hemoglobin(anemia)
- Bone marrow hypercellularity
- Bruising susceptibility(Bruise easily)
- Chronic infection
- Disseminated intravascular coagulation
- Epistaxis(Bloody nose)
- Exertional dyspnea
- Gingival bleeding(Bleeding gums)
- Leukopenia(Decreased blood leukocyte number)
- Muscle weakness(Muscular weakness)
- Pancytopenia(Low blood cell count)
- Low platelet count
- Vertigo(Dizzy spell)
- Weight loss
5%-29% of people have these symptoms
- Abdominal pain(Pain in stomach)
- Bone pain
- Diffuse alveolar hemorrhage
- Gingival overgrowth(Gum enlargement)
- Leukocytosis(Elevated white blood count)
- Lymphadenopathy(Swollen lymph nodes)
- Neutropenia(Low blood neutrophil count)
- Oral cavity bleeding(Bleeding from mouth)
- Productive cough(Wet cough)
- Stomatitis(Inflammation of the mouth)
APL is caused by a chromosomal translocation (rearrangement of material) that occurs in some of the body's cell during a person's lifetime (a somatic mutation ). The translocation involves the fusion of two genes: the ''PML'' gene on chromosome 15 and the ''RARA'' gene on chromosome 17.
The protien produced by this fusion is referred to as PML-RARα. The PML-RARα protein functions differently than what is typically produced by the normal PML and RARA genes.
As a result of the abnormal function, blood cells become "stuck" at the promyelocyte stage and they proliferate (reproduce) abnormally. Excess promyelocytes then accumulate in the bone marrow, disrupting the formation of normal white blood cells and leading to APL. Translocations involving the RARA gene and other genes have been identified in only a few cases of APL.
APL is not inherited . The condition arises from a translocation in some of the body's cells (somatic cells) that occurs after conception. This is referred to as a somatic mutation .Somatic mutations may affect the individual by causing cancers or other diseases, but they are not passed on to offspring.
Acute promyelocytic leukemia can be distinguished from other types of AML based on microscopic examination of the blood film or a bone marrow aspirate or biopsy as well as finding the characteristic rearrangement. The presence of promyelocytes containing multiple Auer rods (termed faggot cells) on the peripheral blood smear is highly suggestive of acute promyelocytic leukemia. Definitive diagnosis requires testing for the PML/RARA fusion gene. This may be done by polymerase chain reaction (PCR), fluorescent in situ hybridization (FISH), or conventional cytogenetics of peripheral blood or bone marrow. This mutation involves a translocation of the long arm of chromosomes 15 and 17. On rare occasions, a cryptic translocation may occur which cannot be detected by cytogenetic testing; on these occasions PCR testing is essential to confirm the diagnosis.
Most cases of APL are treated with an anthracycline chemotherapy drug (daunorubicin or idarubicin) plus the non-chemotherapy drug, all-trans-retinoic acid (ATRA), which is a relative of vitamin A. This treatment leads to remission in 80% to 90% of patients.
Patients who cannot tolerate an anthracycline drug may get ATRA plus another drug called arsenic trioxide. Arsenic trioxide has also proven to be an effective alternative for the 20% to 30% of patients with APL who don't respond to initial treatment or who relapse. If treatment with arsenic trioxide achieves a remission, further courses of this drug may be given.
The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.
- Arsenic trioxide (Brand name: Trisenox)
- Tretinoin (Brand name: Vesanoid®)
Latest research - Acute promyelocytic leukemia
NIH genetic and rare disease info
Acute promyelocytic leukemia is a rare disease.
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