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Acute promyelocytic leukemia

Acute promyelocytic leukemia (APL; AML with t(15;17)(q22;q12) PML/RARα and variants; FAB subtype M3) is a subtype of acute myelogenous leukemia (AML), a cancer of the blood and bone marrow. more...

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In APL, there is an abnormal accumulation of immature granulocytes called promyelocytes. The disease characterized by a chromosomal translocation involving the retinoic acid receptor alpha (RARα) gene and is unique from other forms of AML in its responsiveness to all trans retinoic acid (ATRA) therapy.

Signs and symptoms

Signs and symptoms of acute promyelocytic leukemia are similar to other forms of AML. The accumultation of promyelocytes in the bone marrow results in a reduction in the production of normal red blood cells and platelets resulting in anemia and thrombocytopenia. Either leukopenia or leukocytosis may be observed in the peripheral blood.

Symptoms include:

  • Fatigue, weakness, shortness of breath (from anemia)
  • Easy bruising and bleeding (from thrombocytopenia and coagulopathy)
  • Fever and infection (from lack of normal white blood cells)

In addition, acute promyelocytic leukemia is frequently associated with bleeding caused by disseminated intravascular coagulopathy.

Epidemiology

Acute promyelocytic leukemia represents 5-8% of AML in adults. The median age is approximately 40 years, which is considerably younger than the other subtypes of AML (70 years). The incidence is increased in Latin American countries.

Pathogenesis

Acute promyelocytic leukemia is characterized by a chromosomal translocation involving the retinoic acid receptor-alpha gene on chromosome 17. In 95% of cases of APL, retinoic acid receptor-alpha (RARα) gene on chromosome 17 to the promyelocytic leukemia gene (PML) on chromosome 15.

Four other gene rearrangements have been described in APL fusing RAR to promyelocytic leukemia zinc finger (PLZF), nucleophosmin (NPM), nuclear matrix associated (NuMA), or signal transducer and activator of transcription (STAT) 5b genes.

These fusion proteins disrupt the function of RARα which blocks the normal maturation of granulocytes. Although the chromosomal translocation involving RARa is believed to be the initiating event, additional mutations are required for the development of leukemia.

Diagnosis

Acute promyelocytic leukemia can be distinguished from other types of AML based on morphologic examination of a bone marrow biopsy or aspirate. Definitive diagnosis requires testing for the RARα fusion protein and may be obtained by polymerase chain reaction (PCR), fluorescent in situ hybridization (FISH), or conventional cytogenetics of peripheral blood or bone marrow.

Treatment

APL is unique among the leukemias distinguished by its sensitivity to all-trans retinoic acid (ATRA), a derivative of vitamin A. Treatment with ATRA causes differentiation of the immature leukemic promyelocytes into mature granulocytes. ATRA is typically combined with anthracycline based chemotherapy resulting in a clinical remission in approximately 90% of patients.

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