Acute Promyelocytic Leukema (aPML) - AML/ M3 Subtype - t(15;17) - Vitamin A (ATRA) - Hematology

Medicosis Perfectionalis

24 Jul 201807:29

Summary

TLDRIn this educational video, the host discusses Acute Promyelocytic Leukemia (APL), a subtype of Acute Myelogenous Leukemia (AML). APL is characterized by the t(15;17) translocation, leading to the fusion of PML and RARα genes, causing immature promyelocytes to not mature. The video highlights the importance of recognizing differentiation syndrome and DIC as complications. It also explores unique treatments like using vitamin A to induce maturation and apoptosis of promyelocytes and arsenic trioxide as a novel therapeutic agent. The host poses intriguing questions, such as whether antibiotics can treat cancer, engaging viewers to think critically.

Takeaways

🔬 Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML) characterized by immature cells called promyelocytes.
🧬 The defining feature of APL is the translocation t(15;17), which leads to the fusion of the PML and RARα genes, creating a chimeric protein that disrupts normal cell differentiation.
🩺 APL is classified as M3 subtype of AML and is associated with the presence of numerous Auer rods in blood smears, which is a key diagnostic feature.
⚠️ Disseminated intravascular coagulation (DIC) is a serious complication that can occur in APL patients and is life-threatening.
💊 Vitamin A (retinoic acid) can be used to treat APL by inducing maturation of promyelocytes into mature neutrophils, which then undergo apoptosis.
🚫 Vitamin A does not cause bone marrow suppression, which is a common side effect of chemotherapy.
🌿 Arsenic trioxide is another treatment for APL, showing the remarkable use of a toxic substance in cancer therapy.
🔄 APL's t(15;17) translocation leads to abnormal retinoic acid metabolism, which vitamin A can correct.
👩‍⚕️ Clinical uses of vitamin A include treatment of acne, measles, and retinitis pigmentosa, and it's particularly effective in APL without causing myelosuppression.
🤔 The script poses a question about antibiotics treating cancer, hinting at the complex and sometimes counterintuitive ways different substances can be used in medicine.

Q & A

What is acute promyelocytic leukemia (APL)?
-Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia characterized by the translocation t(15;17). It involves immature promyelocytes that have not matured into myelocytes.
What does the translocation t(15;17) indicate in APL?
-The translocation t(15;17) in APL indicates a chromosomal abnormality where parts of chromosomes 15 and 17 switch places, leading to the fusion of the retinoic acid receptor alpha gene (RARA) on chromosome 17 with the promyelocytic leukemia gene (PML) on chromosome 15.
Why is differentiation syndrome a concern in APL treatment?
-Differentiation syndrome is a concern in APL treatment because it can occur when immature cells mature too quickly, leading to a cytokine release that can cause symptoms like fever, weight gain, and respiratory distress.
How does vitamin A play a role in treating APL?
-Vitamin A, also known as retinoic acid, can induce maturation of the immature promyelocytes into mature neutrophils, which then undergo apoptosis, effectively treating APL. It does not cause bone marrow suppression.
What is the significance of arsenic trioxide in APL treatment?
-Arsenic trioxide is used to treat APL by promoting the degradation of the PML-RARA fusion protein, which is responsible for the block in cell differentiation.
What is the prognosis of APL if differentiation syndrome (DICS) is avoided?
-The prognosis of APL is very good if differentiation syndrome is avoided, as it can be effectively treated with vitamin A and arsenic trioxide.
What are the clinical uses of vitamin A aside from treating APL?
-Aside from treating APL, vitamin A is used to treat conditions like acne, measles to decrease the risk of blindness, and retinitis pigmentosa.
What is the significance of the presence of Auer rods in APL?
-The presence of Auer rods is a characteristic feature of APL and is associated with a high yield on blood smears, indicating the immature promyelocytes.
What is the difference between APL (M3 subtype) and other AML subtypes like M5?
-APL (M3 subtype) is characterized by the presence of Auer rods and the t(15;17) translocation, while M5 subtypes do not have this translocation and may lead to gingival hyperplasia.
What are the initial symptoms that might indicate APL?
-Initial symptoms that might indicate APL include extreme fatigue, mucosal bleeding, anemia, thrombocytopenia, and the presence of blasts on peripheral smear.
What is the best initial therapy for APL with t(15;17) translocation?
-The best initial therapy for APL with t(15;17) translocation is the use of retinoic acid (vitamin A) and arsenic trioxide.

Outlines

00:00

🔬 Acute Promyelocytic Leukemia (APL) Overview

The paragraph introduces acute promyelocytic leukemia (APL), a subtype of acute myelogenous leukemia (AML), characterized by the translocation 15;17. APL is a cancer of the blood and bone marrow, involving immature promyelocytes. It is associated with the presence of Auer rods in blood smears. The paragraph discusses the prognosis of APL, which is generally good unless disseminated intravascular coagulation (DIC) occurs. Vitamin A is highlighted as a treatment for APL as it induces maturation of promyelocytes, leading to apoptosis without causing bone marrow suppression. However, it can cause differentiation syndrome. Arsenic trioxide is also mentioned as a treatment option. The paragraph concludes by explaining the genetic basis of APL, involving the fusion of the retinoic acid receptor alpha gene on chromosome 15 and the promyelocytic leukemia gene on chromosome 17, forming a chimeric protein called PML-RAR alpha.

05:02

💊 Clinical Uses of Vitamin A and APL Treatment

This paragraph delves into the clinical uses of vitamin A, including treatment for acne, measles, and retinitis pigmentosa. It emphasizes that vitamin A does not cause bone marrow suppression, which is a significant advantage in treating APL. The paragraph presents a hypothetical case of a 45-year-old female with symptoms of fatigue, mucosal bleeding, anemia, and thrombocytopenia, and a white blood cell count with 9% blasts, suggesting leukemia. A chromosomal analysis reveals the t(15;17) translocation, leading to the diagnosis of AML M3 subtype. The paragraph concludes with a question about the best initial therapy for APL, highlighting retinoic acid (vitamin A) and arsenic as effective treatments.

Mindmap

Keywords

💡Acute Promyelocytic Leukemia (APL)

Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML). It is characterized by the rapid growth of abnormal white blood cells that do not mature properly. In the video, APL is the central topic, with a focus on its unique features and treatment options. The script mentions that APL is associated with a translocation between chromosomes 15 and 17, which is a key diagnostic feature.

💡Translocation 15;17

Translocation 15;17 is a specific chromosomal abnormality found in APL, where parts of chromosomes 15 and 17 switch places. This translocation leads to the fusion of the PML and RARA genes, creating a chimeric protein that disrupts normal blood cell development. The video script emphasizes the importance of this translocation in the diagnosis and treatment of APL.

💡Myeloblasts

Myeloblasts are immature cells in the myeloid lineage that eventually develop into mature white blood cells. In the context of APL, myeloblasts are affected by the translocation and fail to mature properly, leading to the accumulation of these immature cells in the bone marrow and blood.

💡Auer Rods

Auer rods are abnormal structures found in the cells of patients with APL. They are a characteristic feature of this subtype and can be observed under a microscope in a blood smear. The presence of Auer rods is highlighted in the script as a 'high yield' fact for exams.

💡DIC (Disseminated Intravascular Coagulation)

DIC is a serious complication that can occur in patients with APL. It involves widespread blood clotting, which can lead to severe bleeding and is life-threatening. The script warns that DIC is a 'big deal' and can occur during diagnosis or shortly after chemotherapy, emphasizing the importance of careful monitoring and treatment.

💡Vitamin A (Retinoic Acid)

Vitamin A, also known as retinoic acid, is used in the treatment of APL. It induces the maturation of abnormal promyelocytes into mature neutrophils, which then undergo apoptosis. The video script points out that vitamin A is effective in treating APL without causing bone marrow suppression, which is a common side effect of chemotherapy.

💡Differentiation Syndrome

Differentiation Syndrome, formerly known as Retinol Weak Acid Syndrome, is a potential complication of using vitamin A to treat APL. It involves a systemic inflammatory response and can be life-threatening. The script mentions that this syndrome will be discussed in a future video, indicating its significance in the management of APL.

💡Arsenic Trioxide

Arsenic Trioxide is a chemotherapy drug that is also used to treat APL. Despite being a poison, it has shown efficacy in treating certain types of leukemia, including APL. The script highlights the paradoxical nature of using a toxic substance to treat cancer.

💡Fusion Gene

A fusion gene is created when two separate genes are joined together due to a chromosomal translocation. In APL, the PML and RARA genes fuse to form the PML-RARA fusion gene, which is central to the disease's pathogenesis. The script explains that this fusion gene disrupts normal cell differentiation and metabolism.

💡Chromosomal Analysis

Chromosomal analysis is a diagnostic test that examines the chromosomes within cells to identify abnormalities. In the script, chromosomal analysis is used to confirm the presence of the t(15;17) translocation, which is diagnostic for APL. This test is crucial for accurate diagnosis and appropriate treatment planning.

💡Bone Marrow Suppression

Bone marrow suppression refers to the decrease in the production of blood cells by the bone marrow, often as a side effect of chemotherapy. The script contrasts this with the use of vitamin A in APL treatment, which does not cause bone marrow suppression, making it a more favorable treatment option.

Highlights

Acute promyelocytic leukemia (APL) is a specific subtype of acute myelogenous leukemia (AML).

APL is characterized by translocation 15;17, affecting immature promyelocytes.

APL is a cancer of the blood and bone marrow, involving multipotent stem cells.

Myeloblasts and monoblasts are key cells affected in APL.

APL is subtype M3 of AML, with the presence of numerous Auer rods in blood smears.

DIC (disseminated intravascular coagulation) is a serious complication of APL.

APL has a good prognosis unless DIC occurs.

Vitamin A can be used to treat APL by inducing maturation of promyelocytes.

Vitamin A does not cause bone marrow suppression, unlike chemotherapy.

Vitamin A can lead to differentiation syndrome.

Arsenic trioxide is another treatment for APL.

The t(15;17) translocation leads to the fusion of RARα and PML genes, forming the PML-RARα fusion gene.

Vitamin A, also known as retinoic acid, can treat APL by correcting abnormal retinoic acid metabolism.

Clinical uses of vitamin A include treatment of acne, measles, and retinitis pigmentosa.

A 45-year-old female with fatigue, mucosal bleeding, anemia, and thrombocytopenia could be diagnosed with APL.

Chromosomal analysis revealing t(15;17) translocation confirms the diagnosis of APL.

DIC is a common complication of APL.

Initial therapy for APL includes retinoic acid (vitamin A) and arsenic trioxide.