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28 Cards in this Set
- Front
- Back
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Activating mutations result in _______.
List 3 examples of such mutations. How many mutations are required? |
Activating mutations result in autonomous cell proliferation.
Ex: FLT3, Ras, c-Kit. Only need 1 mutation, not several! |
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FLT3:
What is it? Effect of mutation? (General and Disease) |
FLT3 is a tyrosine kinase receptor
When mutated, it is constitutively activated and 25-35% of mutations results in ACUTE MYELOGENOUS LEUKEMIA. Poor prognosis. |
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What percentage of patients with AML have abnormal karyotypes?
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About half.
Roughly half have normal chromosomal structures. But just because chromosomes are normal, doesn't mean they don't have mutations! |
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What is the most common genetic lesion in AML in someone with a NORMAL karyotype?
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Nucleophosmin (NPM-1); present in 50-60% of pts w/CN-AML (cytogenetically normal-AML)
i.e., normal karyotype |
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Role of nucleophosmin.
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Nucleocytoplasmic shuttling protein that is localized in nucleolus.
Interacts with p53 (cell prolifern, apoptosis) Involved in DNA repair and CENTROSOME duplication Ribosome biogenesis |
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How would you distinguish between AML and ALL morphologically?
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AML: Myeloid blasts have cytoplasmic granulation
ALL: Lymphoblasts are smaller and look like lymphocytes, no granulations |
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What are Auer rods? Indicative of?
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Crystallized granules pathognomonic of AML
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Myeloperoxidase Stain:
What does it stain? Which leukemia tests positive? |
Stains MPO present in primary granules.
AML; myeloid blasts contain myeloperoxidase |
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Sudan Black Stain:
What does it stain? Which leukemia tests positive? |
Sudan Black stains lipid particles in primary and secondary granules.
Myeloid blasts: positive; AML Lymphoblasts negative. |
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Tdt+:
Which leukemia might express this? |
Lymphoid
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Immunophenotype of HSC.
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CD34+
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Immunophenotype of Myeloid Progenitor.
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CD13 and/or CD33
AML!!! |
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Immunophenotype of Lymphoid Progenitor.
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Tdt and B/T cell markers (ALL OF THEM)
ALL |
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Describe each stage of the FAB classification system (M0-M7).
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M0: Undiff'd
M1: Myeloblastic M2: Myeloblastic w/diff M3: Promyelocytic M4: Myelomonocytic M5: Monocytic M6: Erythroleukemia M7: Megakaryocytic |
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This AML is associated with DIC.
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AML M3: Acute Promyelocytic Leukemia
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AML M3:
Pathognomonic translocation Effect of translocation Treatment |
translocation(15; 17)
Results in novel fusion protein: PML-RAR (retinoic acid receptor) Tx: Oral all-trans retinoic acid (differentiation tx) |
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What is the role of retinoic acid receptor in differentiation?
Effect of t(15;17) translocation? |
In normal cells, retinoic acid binds NUCLEAR retinoic acid receptor and promotes assocn of transcriptional activation complex (Histone Acetyl Transferase--HAT)
This results in the acetylation of histones and unwinding of DNA. Facilitates transcription of downstream genes impt for normal diff and maturation of heme progenitors. Translocation causes abnormal PML-RAR fusion protein. When RA binds this receptor, Histone Deacetylase Binds along with co-repressors. This inhibits unraveling of histones, prevents DNA transcription, and consequently prevents differentiation. |
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All-Trans Retinoic Acid (ATRA):
Use MOA |
Use in Acute Promyelogenic Leukemia (M3)
Binds PML-RAR fusion protein and allows HAT to bind. This permits malignant cells to mature and differentiate. |
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Non-Specific Esterase:
What does it stain? Which leukemia tests positive? |
Stains non-specific esterase
M4, M5 leukemias test positive because you'd expect non-specific esterases in monocytic granules. (M4 = Acute myelomonocytic; M5 = Acute monocytic) |
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Extramedullary Infiltration:
What is it? Which specific leukemia exhibits it? |
M4, M5: leukemic involvement (invasion with blasts) on gum, CNS, LNs, SKIN
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This SPECIFIC leukemia is common in children with Down's Syndrome.
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M7
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Acute Lymphoid Leukemia:
What cells are affected? Where does this occur? What stage are cells arrested in? |
Affects early precurors of B and T cell lymphocytes
Occurs in BM Arrested in lymphoblast stage |
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What is the commonest form of leukemia in children?
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Acute Lymphoid Leukemia; peaks ages 2-4
Incidence decreases after age 10, rises after 40 |
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Describe the FAB classification of lymphoid leukemias (L1-L3).
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L1: small uniform cells; pediatric type
L2: large varied cells, mostly adult L3: large varied cells w/vacuoles; Burkitt's leukemia |
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Which lymphoid leukemia is HIGHLY curable?
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L1 (pediatric)
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What cell type is involved in acute lymphoid leukemia in 85% of cases?
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Pre-B cells (BM)
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What cell type is involved in acute lymphoid leukemia in 20% of cases?
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Pre-T cells (LOCATED IN THYMUS!!!!)
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Pre-B Cell Leukemia:
Location Cytogenetic Phenotype |
Located in BM
Tdt+ CD19+, CD20+ |
