Philadelphia Chromosome USMLE Notes & Mnemonics contains all the high-yield points you need to know.
Definition:
- Philadelphia Chromosome: A specific chromosomal abnormality that is a hallmark of chronic myeloid leukemia (CML). It results from a translocation between chromosomes 9 and 22, denoted as t(9;22)(q34;q11). (Ref)
Pathophysiology:
- This translocation creates a fusion gene called BCR-ABL, which encodes a protein with tyrosine kinase activity. This abnormal protein leads to uncontrolled cell division, characteristic of CML.
Epidemiology:
- Commonly associated with CML but can also be seen in acute lymphoblastic leukemia (ALL) and occasionally in acute myeloid leukemia (AML).
Clinical Features:
- Often asymptomatic in early stages.
- Symptoms, when they occur, are typically related to anemia, leukocytosis, or splenomegaly.
Diagnosis:
- Cytogenetics: Detection of the t(9;22) translocation.
- FISH (Fluorescence In Situ Hybridization): To detect BCR-ABL fusion.
- PCR (Polymerase Chain Reaction): Highly sensitive for detecting BCR-ABL transcripts.
Treatment:
- Tyrosine Kinase Inhibitors (TKIs): Imatinib (first-line), dasatinib, nilotinib. These drugs specifically target the BCR-ABL protein.
- Allogeneic Stem Cell Transplantation: Considered in some patients, particularly those who do not respond to TKIs.
Prognosis:
- Dramatically improved with the advent of TKIs. Many patients achieve long-term remission.
Mnemonic: “PHILadelphia”
- Ph+ chromosome (Philadelphia chromosome positive)
- Hematologic cancer (CML)
- Imatinib treatment
- Long arm translocation (Long arms of chromosomes 9 and 22)
Chart: Philadelphia Chromosome in CML
| Feature | Description |
|---|---|
| Chromosomal Abnormality | t(9;22)(q34;q11) |
| Resultant Fusion Gene | BCR-ABL |
| Associated Disease | Chronic Myeloid Leukemia (CML) |
| Diagnostic Tests | Cytogenetics, FISH, PCR |
| Treatment | Tyrosine Kinase Inhibitors (e.g., Imatinib) |
| Prognosis | Improved with TKIs, potential for long-term remission |
Note: For the USMLE, it’s crucial to recognize the association of the Philadelphia chromosome with CML and the role of TKIs in treatment. The diagnosis often involves a question stem describing a patient with signs and symptoms of CML and laboratory findings suggestive of the Philadelphia chromosome. Understanding the mechanism of action and clinical use of TKIs in managing CML is also frequently tested.
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