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Flashcards in CML case Deck (23)
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1

Reciprocal translocation occurs where in the BCR-ABL protein and forms what?

22 and 9
Fusion gene

2

BCR (breakpoint cluster gene)

Housekeeping gene that's always on

3

ABL (Abelson leukemia)

Proto-oncogene that codes for a non-receptor TK found in the cytoplasm and nucleus

4

What must happen for ABL to be an oncogene?

ABL binds to BCR

5

What occurs in CML resulting in BCR-ABL fusion?

Chimeric protein w/ strong and constitutive TK activity

6

What proto-oncogenic pathways that compound the production of cancer cells?

RAS, PLK3, JAK/STAT

7

Imatinib (Gleevec)

Competitive inhibitor
Block binding of ATP to BCR-ABL tyrosine kinase, inhibiting it's activity

8

What happen to the onocgene activity if TK is blocked?

Substrate required for BCR-ABL function cannot be phosphorylated and cellular events don't occur

9

What are the side effects to imatinib?

Hematological - neutropenia, thrombocytopenia, anemia
Non-hematological - superficial edema, nausea, headache

10

Imatinib resistance

Mutation so that the cell blocks enzymatic site so drug cannot bind
Mutation leads to active receptor T315I

11

Ponatinib

Only drug that is effective against T315I mutation
Currently inhibits all mutated &
unmutated forms of BCR-ABL

12

Omacetaxine mepesuccinate

Binds 80S ribosome, no chain elongation

13

Busulfan

Alkylating agent
Bone marrow depression (stem cells)

14

IFN α-2b

Inhibits cell proliferation, interferes w/ oncogene expression, enhances immune activities
(↑macrophage phagocytosis & augments T cell cytotoxicity)

15

Cyclophosphamide

Alkylating agent (nitrogen mustard): puts alkyl group on guanine – crosslinking interferes w/ DNA 
can’t unwind, replicate, or transcribe
Cardiotoxicity, hemorrhagic cystitis, hematuria (co-administer w/ MESNA to prevent bladder burn)

16

Mechlorethamine

Alkylating agent (nitrogen mustard): puts alkyl group on guanine – crosslinking interferes w/ DNA
Can’t unwind, replicate, or transcribe
Unstable (most reactive)

17

Cytarabine

2’-deoxycytidine analog; no base rotation, no chain elongation, DNA polymerase inhibition
Bone marrow depression

18

What are some common reaction in graft vs host response

Diarrhea, erythema, dispigmentation, weight loss, malaise, fever, joint pains
Eventual death

19

What does graft vs host response do?

Infections due to immunosuppressive regimens – viral, bacterial fungal

20

How is graft vs host disease minimized?

Careful patient preparation & best ABO-compatible HLA match
Multi-tiered approach to immunosuppressive drug therapy

21

Methotrexate

Folic acid antagonist
Azotemia, systemic bacterial infection of blood or tissues, GI bleeding, ↓WBC & platelets,
inflammation of mucosal surfaces

22

Cyclosporine

Blocks transcription of cytokine genes in activated T cells
Nephrotoxicity, hypertension

23

Tacrolimus

Binds FK506; complex inhibits calcineurin phosphatase
Inhibits Ca2+ dependent events (e.g. degranulation, apoptosis)
Nephrotoxicity, hyperglycemia, diabetes, neurotoxicity