FOM 6.1.1 Flashcards
Give a brief description of Ms. Marion Osei and her diagnosis.
43 y/o, female, African American, business woman, anxious about recent diagnosis, acute promyelocytic leukemia (APL).
What two medications are suggested by her oncologist?
Vesanoid (All-trans retinoic acid) and Trisenox (arsenic trioxide)
Describe the survival % of the three levels of severity (low, med, high) of acute promyelocytic anemia.
Low: 98%
Med: 89%
High: 70%
In essence, the prognosis for this form of cancer is very good. The earlier the cancer diagnosis is reached, the more the chance of survival approaches 100%.
What are auer rods (used to aid in diagnosis of APL)?
Fuzed azurophilic granules
What are the two proteins are fused in APL? Their individual functions?
PML: growth suppressor that induces cell death and aids in cell cycle regulation
RARα: Induces normal differentiation by dissociated from repressor complexes at physiological ATRA (all-trans retinoic acid)
What is the mechanism of the fused protein, PML-RARα?
Oncogenic protein that blocks myeloid differentiation at promyelocyte stage.
1) inhibits apoptosis (inhibitis GM-CSF signals)
2) inhibits normal cell differentiation (doesn’t dissociate from receptor at physiological [ ] of ATRA
What is the mechanism of action of Vesanoid (All-trans retinoic acid) and Trisenox (arsenic trioxide)?
Both drugs work to cause dissociation of PML-RARα from differentiation gene repressors
What are the the three types of possible diagnostic tests? Which is best?
BM aspirate
Fluorescent In-Situ Hybridization (FISH) - Best 😎
Immunohistochemistry
What are the 3 main actions of vesanoid (ATRA)
decrease cell proliferation, inhibit telomerase, promotion growth/differentiation of normal cells in BM
What are some possible side effects of Vesanoid (ATRA)?
embryotoxic, Vit A toxicity, Retinoic acid syndrome
What is the main effect of Trisenox (Arsenic Trioxide) since the mechanism is completely understood?
Damage/degrades fusion protein PML-RARα
What are some potential side effects of Trisenox (Arsenic Trioxide)?
Nausea, vomiting, fever, APL differentiation syndrome (Cytokine storm- fever, chills, sudden weight gain)
Estrogen binding estrogen receptors (ER) allows for dimerization that recruits HAT enzymes, which would activate transcription. Tamoxifen binds ERs as well, why would it be a useful drug in treating cancer?
Tamoxifen is structurally different. So much so, that is causes dimerization of ERs that recruit HDAC enzymes, which actively repress transcription. Thus, it is beneficial in forms of breast cancer that express estrogen receptors.
Why is tamoxifen effective in the treatment of uterine cancer?
Uterine cancers don’t express ERs (tissue specificity is an important factor)
