Final Exam Flashcards
What are the two main causes of chromosome abnormalities?
- Altering the concentration of gene products (dupliate/amplify or delete/interrupt)
- Altering the gene product itself (fuse regulatory regions or fuse functions)
Why does the BCR/ABL1 translocation cause CML?
- The ABL1 tyrosine kinase produced by the fusion is permanently turned on, activates signal pathways
- Leads to malignant transformation
What diagonstic assays can be used to identify the t(9;22) translocation (BRC/ABL1)?
- Karyotyping (long 9 and short 22)
- BCR-ABL1 dual color dual fusion assay (FISH)
How does Imatinib (and other TKIs) work to cause remission in CML?
- Blocks the ATP binding center of BCR-ABL1 kinase
- This block phosphorylation of proteins
- No more uncrontolled growth and cell signaling
How should CML patients be treated when they have blast crisis with first-line TKI or no response to second TKI?
BM/SC Transplantation (only true cure)
How is CML and some other diseases monitored?
- Use of Interphase FISH assay & karyotyping
- Interphase FISH looks at many cells when they are not actively dividing
- Look for abnormal cells (co-localization of BCR/ABL)
What is the benefits of karyotype monitoring in disease progression over FISH?
- Can detect new chromosome abnormalities that arise
- This tells you if the disease is getting worse or remaining in remission
What is a common chromosomal abnormality with AML?
- MLL (KMT2A) gene
- Also known as 11q23.3 (location)
- Also known as t(4;11) translocation
What is the difference between dual fusion FISH and break apart FISH?
- Dual Fusion: Co-localization tells you that there is an abnormality (translocation causes 2 known gene regions to be in same area)
- Break Apart: Co-localization is normal, abnormality is when the 5’3’ region of a gene is no longer in same area (use when there are many gene partners for a translocation)
What is one of the limitation of break apart FISH?
It does not tell you what the partner chromsome/locus is in the translocation, just that an abnormality has occured
What are some of the limitation of chromsome microarray?
- Balanced rearrangements (no gain or loss present)
- Low level mosaicism/clonal evolution (minimal residual disease, minor clones, less than 10-15%)
What are some of the benefits of chromosome microarray?
- Can detect cytogenetic abnormalities missed by traditional cytogenetics
- Rearrangements below level of G-band detection (really small deletions!)
- Copy number neutral loss of heterozygosity or acquired homozygosity (SNP microarray)
What is a common finding in all types of leukemia?
Copy number neutral loss of heterozygosity or acquired homozygosity
What are the 4 key fungal cell structures?
What is the difference between septate and aseptate hyphae?
- Spetate have clear cell walls
- Aspetate get longer without clear divisions
What kind of infections are encapsulated fungi associated with?
Often associated with meningitis due to CNS infiltration
What is an important structure formed by yeast (particularly candida)?
- A germ-tube (outgrowth produced by spores of spore-releasing fungi during germination)
- Creates somatic hyphae
What is a dimorphic fungus?
Converts between yeast and hyphae
What arm of adaptive immunity is important for fungal infections?
- Fungal infections occur with impaired cell-mediated immunity (AIDS/HIV)
- So, you need T cells!
- Humoral immunity is not so much needed (B cells)
What fungi is this?
Candida
What fungi is this?
Cryptococcus
What fungi is this?
Aspergillus
What fungi is this?
Mucor & Rhizopus
What fungi is this?
PCP
What are some risk factors for fungal infections?
- Neutropenia (or dysfunction)
- HIV/AIDS
- T cell deficency
- Transplantation
- Immunosuppressive Therapy
- Antibacterial Therapy
- Uncontrolled Diabetes
What is the target of the following antifungal agents?
- Polyenes
- Azoles
- Echinocandins
- Pyrimidine Analogues
- Polyenes- ergosterol (forms pores in membrane)
- Azoles- inhibits ergosterol synthesis
- Echinocandins- inhibits beta-glucan synthesis
- Pyrimidine Analogues- inhibits fungal thymidine synthesis
What are the uses of the following antifungal agents?
- Polyenes
- Azoles
- Echinocandins
- Pyrimidine Analogues
- Polyenes- broad spectrum
- Azoles- broad spectrum
- Echinocandins- yeast and molds (not dimorphics)
- Pyrimidine Analogues- yeasts only (often with resistance)
What are some examples of the following antifungal agents?
- Polyenes
- Azoles
- Echinocandins
- Pyrimidine Analogues
- Polyenes- amphotereicin B, nyastatin
- Azoles- anything ending with -azole
- Echinocandins- anything ending with -fungin
- Pyrimidine Analogues- 5-FC
What chemotherapeutic agent is associated with pulmonary toxicity?
- Bleomycin
- Cuases stimulation of lung fibroblasts leading to fibrosis
- Also hypersensitivity pneumonitis
What is the action of most breast cancer chemotherapies?
- Anti-estrogens (Tamoxifen)
- Aromatase inhibitors (Anastrazole)
What is the action of most prostate cancer chemotherapies?
- All work to decrease testosterone or its effects
- Antiandrogens (Flutamide)
- LHRH agonists (Leuprolide)
- GnRH antagonists
- CYP17 inhibitors
What are the 4 monoclonal antibodies and targets you need to know?
- Rituximab, CD20, lymphoma
- Trastuzumab, Her-2, breast cancer
- Cetuximab, EGFR, solid tumors
- Bevacizumab, VEGF, solid tumors
What are some symptoms of Bevacizumab and cetuximab?
- Bevacizumab- proteinuria, GI perforation, hypertension
- Cetuximab- severe hypersensitivity (chimeric) and acneiform rash (increased survival)
What are 3 immunotherapy agents used in cancer to reactivate T cells?
- Ipilimumab- Anti CTLA4
- Pembrolizumab- Anti PD1
- Nivolumab- Anti PD1
What is responsible for the acute clinical symptoms in acute lytic viral infections?
- Tissue destruction due to virus replication
- Side effects of host immune response
What are some main differences between acute and chronic lytic viral infections??
- Acute- short time course (3-14d), lysis of infected cell with progeny production
- Chronic- continual infection/re-infection cycle, does not result in cell lysis
What are some characteristics of viral nucleic acid during latency?
- Both RNA and DNA viruses can establish latency
- All latent viruses maintain genome as DNA
- Genome can be integrated (provirus)
- Genome can be extrachromosomal (episome)
What is the site of latency for EBV and CMV?
- EBV- lymphoid cells
- CMV- various cells
How does EBV infect?
- Infects B cells via CD21 complement receptor
- Results in atypical lymphocytes
- Production of heterophile antibodies
What are some EBV associated diseases?
- Life-threatening in X-linked lymphoproliferative syndrome
- Hairy Leukoplakia in immunocompromised
- Burkitt’s lymphoma (HIV associated)
How does EBV transform in the body?
- Latency via episomal DNA in B cells
- Increases IL-10 (more proliferation)
What is a significant marker of CMV?
Owl eyes or aliens around mucosal areas
How does CMV establish latency?
Unstable MHC-1 in infected cells, so can’t be recognized by CD8+ T cells
What are some clinical findings with CMV?
- “Blueberry muffin” lesions
- Heterophile-negative mono
- Risks in transplant patients
- Infections in AIDS patients
