5 Questions
What is the characteristic chromosomal abnormality observed in Acute Promyelocytic Leukemia (APL) and how does it affect the genome?
The characteristic chromosomal abnormality in APL is the translocation t(15;17)(q22;q21), which results in the fusion of the PML gene on chromosome 15 with the RARA gene on chromosome 17. This fusion leads to the formation of a chimeric PML-RARA gene, which is a hallmark of APL and affects the genome by disrupting normal cellular differentiation and proliferation.
What is the role of Fluorescence in situ Hybridization (FISH) in the diagnosis of Acute Promyelocytic Leukemia (APL)?
FISH is a molecular cytogenetic technique used to detect the PML-RARA fusion gene in APL, allowing for the identification of the characteristic t(15;17) translocation and confirming the diagnosis of APL.
How does the karyotype analysis of a normal male individual (46,XY) differ from that of an individual with Acute Promyelocytic Leukemia (APL)?
A normal male karyotype is 46,XY, whereas an individual with APL typically has a karyotype of 46,XY,t(15;17)(q22;q21), indicating the presence of the characteristic chromosomal translocation.
What is the prognosis of Acute Promyelocytic Leukemia (APL) in terms of treatment response and survival rates?
APL has a relatively good prognosis, with a high response rate to treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), and a 5-year survival rate of approximately 80-90%.
What is the significance of uniparental isodisomy in the development of Acute Promyelocytic Leukemia (APL)?
Uniparental isodisomy, a rare genetic event, can lead to the formation of a cryptic insertion of RARA into PML on chromosome 15, resulting in the development of APL.
Study Notes
Karyotyping in Acute Promyelocytic Leukemia (APL)
- Karyotyping is essential in the initial workup of APL to detect rare molecular subtypes and additional cytogenetic abnormalities.
- The characteristic t(15;17) translocation in APL involves the PML gene on chromosome 15 and the RARA gene on chromosome 17, resulting in a fusion gene that produces the PML-RARα protein.
Fluorescence In Situ Hybridization (FISH)
- FISH is a powerful molecular cytogenetic technique that uses fluorescent probes to detect and localize specific DNA sequences on chromosomes.
- In APL, FISH can detect the PML-RARA fusion gene using dual probes that bind to the breakpoint on chromosomes 15 and 17.
- A normal FISH result shows two red and two green signals, indicating lack of rearrangement of chromosomes 15 and 17.
- A positive FISH result shows a dual color and fusion of the colors, indicating the PML-RARA fusion gene.
Bone Marrow Smear Workup of APL
- Bone marrow smear workup of APL is hypercellular, with APL promyelocytes accounting for about 30% of the myeloid cells in the classic variant.
- Promyelocytes have a characteristic creased, folded, bilobed, kidney-shaped, or dumb-bell shaped nuclei with a high nucleus-cytoplasmic ratio, fine chromatin, and prominent nucleoli.
- There is a decrease in the number of mature granulocytes and erythroid precursors, and an increase in condensed chromatin and pseudo-Pelger-Huet cells.
- Many violet granules coalesce to form Auer rods.
Karyotyping Steps
- Cell collection
- Cell arrest
- Fixation
- Staining
- Cell culture
- Hypotonic treatment
- Slide preparation
- Microscopy
This quiz covers the importance of karyotyping in the initial diagnosis of acute promyelocytic leukemia, including the detection of rare molecular subtypes and characteristic translocations.
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