Acute Promyelocytic Leukemia (APL, AML-M3)

Definition

A distinct subtype of acute myeloid leukemia (AML) characterized by:

• Genetic hallmark: t(15;17) translocation → PML::RARA fusion gene (blocks myeloid differentiation).
• Morphology: Accumulation of abnormal promyelocytes (Auer rods common).

Key Features

1. Medical Emergency:
   1. High risk of disseminated intravascular coagulation (DIC) and fatal hemorrhage due to:
   2. Release of procoagulants from granules in malignant promyelocytes.
2. Treatment:
   1. ATRA (All-Trans Retinoic Acid) + Arsenic Trioxide (ATO):
   2. Targets the PML::RARA fusion protein → Forces differentiation of leukemic blasts.
   3. Chemo avoided initially (can worsen DIC; reserved for high-risk cases).
3. Prognosis:
   1. Highly curable (>90% survival with modern therapy).
   2. Requires urgent diagnosis (morphology + FISH/PCR for PML::RARA).

Definition

APL is a subtype of acute myeloid leukemia (AML) characterized by the accumulation of abnormal promyelocytes in the bone marrow and peripheral blood.

Genetic Hallmark

• t(15;17)(q24;q21) translocation
• Forms the PML-RARA fusion gene
• This disrupts retinoic acid signaling, which is essential for myeloid differentiation.

Pathophysiology

• PML-RARA fusion protein blocks the maturation of myeloid precursors at the promyelocyte stage.
• Leads to accumulation of immature promyelocytes.
• Abnormal promyelocytes express tissue factor, triggering disseminated intravascular coagulation (DIC).

Clinical Features

• Presents acutely, often in young adults
• Symptoms due to cytopenias:
  • Anemia → fatigue
  • Thrombocytopenia → mucosal bleeding, petechiae
  • Neutropenia → infections
• Bleeding and DIC are common and can be life-threatening
  • Look for oozing from venipuncture sites, bruising, hematuria

Diagnosis

• Peripheral smear: Promyelocytes with multiple Auer rods (“faggot cells”)
• Confirmatory test: Detect PML-RARA fusion via RT-PCR or FISH

Treatment (Start immediately if suspected)

• All-trans retinoic acid (ATRA): Induces differentiation
• Arsenic trioxide (ATO): Degrades PML-RARA fusion protein
• Supportive care: Platelets, cryoprecipitate, manage DIC
• Watch for Differentiation Syndrome (fever, pulmonary edema, hypotension → treat with steroids)

Prognosis

• With early recognition and appropriate treatment, APL is highly curable
• >90% remission rates in low- and intermediate-risk patients

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