Acute Promyelocytic Leukemia (APL) Pathogenesis

Study Notes

Pathogenesis

Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML)
Characterized by a chromosomal translocation, t(15;17), which leads to the fusion of the PML gene on chromosome 15 with the RARA gene on chromosome 17
This fusion protein (PML-RARA) disrupts normal hematopoiesis, leading to the proliferation of immature myeloid cells
PML-RARA also inhibits the differentiation of promyelocytes, causing them to accumulate in the bone marrow

Cytogenetics

The t(15;17) translocation is present in >95% of APL cases
The PML-RARA fusion protein is detectable in nearly all APL cases
Other chromosomal abnormalities, such as trisomy 8, may be present in up to 20% of cases
Cytogenetic analysis is essential for diagnosis and monitoring of APL

Prognosis

APL has a high cure rate, with overall survival rates of 80-90% in modern treatment protocols
Early diagnosis and treatment are crucial, as APL can progress rapidly and lead to bleeding complications
Factors that affect prognosis include:
- Age: older patients have a poorer prognosis
- WBC count: higher counts are associated with a poorer prognosis
- Presence of secondary chromosomal abnormalities: may indicate a poorer prognosis

Treatment Options

All-trans retinoic acid (ATRA) is a key component of APL treatment, as it induces differentiation of promyelocytes
ATRA is often combined with chemotherapy, such as anthracyclines and cytarabine
Arsenic trioxide is also used in the treatment of APL, particularly in patients who are resistant to ATRA
Stem cell transplantation may be considered in some cases, particularly in those with high-risk disease

Clinical Presentation

APL often presents with symptoms related to bleeding complications, such as:
- Easy bruising
- Petechiae
- Ecchymoses
- Hemorrhage
Other common symptoms include:
- Fatigue
- Weight loss
- Fever
- Bone pain
Laboratory findings typically include:
- Anemia
- Thrombocytopenia
- Leukocytosis with abnormal promyelocytes
- Coagulopathy, including disseminated intravascular coagulation (DIC)

Pathogenesis

Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) characterized by a chromosomal translocation, t(15;17)
t(15;17) translocation leads to the fusion of the PML gene on chromosome 15 with the RARA gene on chromosome 17, forming a PML-RARA fusion protein
PML-RARA fusion protein disrupts normal hematopoiesis, causing proliferation of immature myeloid cells and accumulation of promyelocytes in the bone marrow

Cytogenetics

t(15;17) translocation is present in >95% of APL cases
PML-RARA fusion protein is detectable in nearly all APL cases
Other chromosomal abnormalities, such as trisomy 8, may be present in up to 20% of cases
Cytogenetic analysis is essential for diagnosis and monitoring of APL

Prognosis

APL has a high cure rate, with overall survival rates of 80-90% in modern treatment protocols
Early diagnosis and treatment are crucial to prevent bleeding complications
Prognosis is affected by age, with older patients having a poorer prognosis
WBC count and presence of secondary chromosomal abnormalities also impact prognosis

Treatment Options

All-trans retinoic acid (ATRA) induces differentiation of promyelocytes and is a key component of APL treatment
ATRA is often combined with chemotherapy, such as anthracyclines and cytarabine
Arsenic trioxide is used in APL treatment, particularly in patients resistant to ATRA
Stem cell transplantation may be considered in high-risk disease cases

Clinical Presentation

APL often presents with symptoms related to bleeding complications, such as easy bruising, petechiae, ecchymoses, and hemorrhage
Fatigue, weight loss, fever, and bone pain are common symptoms
Laboratory findings typically include anemia, thrombocytopenia, leukocytosis with abnormal promyelocytes, and coagulopathy, including disseminated intravascular coagulation (DIC)

Description

Learn about the pathogenesis of Acute Promyelocytic Leukemia, a subtype of Acute Myeloid Leukemia, including its chromosomal translocation and effects on hematopoiesis. Discover how the PML-RARA fusion protein disrupts normal cellular processes.