Part 1 Flashcards
Histone synthesis occurs during __ phase
S
CpG islands in DNA _______ transcription
Represses
The template strand of DNA is methylated at ________ and _______ bases allowing recognition of the template in replication
cytosine and adenine
Histone acetylation __________ transcription.
increases/allows
Amino acids required for purine synthesis
glycine, aspartate, glutamine
Leflunomide
Disrupts pyrimidine syntesis by inhibit dihydroorotate dehydrogenase.
Methotrexate
Inhibits Dihydrofolate reductase, inhibiting pyrimidine sythesis
Trimethoprim
Inhibits Dihydrofolate reductase, inhibiting pyrimidine sythesis
Pyrimethamine
Inhibits Dihydrofolate reductase, inhibiting pyrimidine sythesis
5-fluorouracil
inhibits pyrimidine synthesis by forming 5-f-dUMP.
6 mercaptopurine
prodrug is azathioprine, inhibits purine syntesis.
Mycophenolate
inhibits inosine monophosphate dehydrogenase and thus guanine synthesis.
Ribavirin
inhibits inosine monophosphate dehydrogenase and thus guanine synthesis.
Hydroxyurea
interrupts both purine and pyrimidine synthesis by inhibiting ribonucleotide reductase.
Lesch-Nyhan Syndrome
Absent HGPRT, no purine salvage. H: hyperurecemia G: gout P: pissed off (aggressive and selfmutilating) R: retardation T: dysTonia Tx: Allopurinol
Nucleotide excision repair
endonuclease release the damaged bases, filled in by DNA pol and ligase. Repairs bulky helix distorting mutations. Occurs in G1. Defective in Xeroderm pigmentosum.
Base Excision Repair
Glycosylase removes, Endonuclease removes an additional and cleaves 5’ end, Lyase cleaves 3’ end, DNA pol fills in the gap and DNA ligase seals. Occurs throughout cell cycle. GEL PLease
Mismatch Repair
Occurs in G2 mostly, defective in Lynch Syndrome (heriditary nonplyposis colorectal cancer)
Nonhomolgous end joining
DNA lost in the process usually. Defective in ataxia telangiectasia, BRCA1, and Fanconi anemia.
Stop codons
UGA UAG UAA
RNA Pol I
makes rRNA
RNA pol II
makes mRNA
RNA pol III
makes tRNA
tRNA
70-90 nucleotides, Amino acid bound to 3’ end at the CCA sequence. T arm (nearest to 3’ end) tethers to the ribosome. D arm detects the aminoacyl tRNA synthetase.
Thyroid Papillary Carcinoma
Most common, childhood exposure to radiation, Orphan Annie eyed nuclei w/ nuclear grooves, psamomma bodies, good prognosis
Thyroid Follicular Carcinoma
Fibrous capsule with invasion. Not distinguishable with FNA. One of four cancers that spread hematogenously.
4 Cancers that spread hematogenously
Thyroid Follicular Carcinoma, RCC, HCC, Choriocarcinoma
Thyroid Medullary Carcinoma
Malignant Proliferation of parafollicular C cells. High levels of Calcitonin may cause hypocalcemia. Calcitonin amyloid. Associated with MEN2A/MEN2B (RET)
Thyroid Anaplastic Carcinoma
Undifferentiated malignant tumor, found in the elderly, often invades local structures (Airway), poor prognosis.
Parathyroid Adenoma
Bening, releases PTH which may cause nephrolithiasis, nephrocalcinosis, CNS disturbances, constipation, peptic ulcer disease, pancreatitis, osteitis fibrosa cystica.
Human Placental Lactogen (hPL)
Causes pancreatic beta cell proliferation in the 3rd trimester, increases maternal lipolysis, enhances ketogenesis, and decreases maternal glucose use.
Estriol
Dominant estrogen in 3rd trimester, requires contribution from fetal adrenals and liver.
Segemented Viruses
BOAR: Bunya, Orthomyxo, Arena, Reo
B-ALL
CD10, CD19, CD20+ excellent response to CTX. Associated with t(12:21) and t(9:22).
T-ALL
CD2-CD8+, presents as thymic mass in teenage.
AML
Several subtypes, MPO seen as Auer rods, average onset at 50-60
Acute Promyelocytic Leukemia
Subtype of AML, t(15:17), mutation in the rentinoic acid receptor, Auer rods may cause DIC. Tx: All-trans retinoic acid, which causes blasts to mature.
Acute Monocytic Leukemia
Subtype of AML, monoblasts will infiltrate gums
Acute Magekaryoblastic Leukemia
Subtype of AML, no MPO, associated with Down Syndrome after the age of 5.
Myelodysplastic syndrome
Cytopenias with hypercellular bone marrow. Blasts increased by lower than 20%. High risk of fatal infection or bleed. May progress to leukemia.
CLL
Naive B cells CD5 and CD20+, smudge cells on blood smear, can cause a lymphoma in the LN, hypogammaglobulinema, autoimmune hemolytic anemia,. Can progress to large B cell lymphoma.
Hairy Cell Leukemia
Mature B cells with “hairy” cytoplasmic processes. TRAP+. Spenlomegaly restricted to red pulp, dry bone marrow tap, usually no LAD. Tx: 2-CDA
Adult T cell Leukemia/Lymphoma
CD4+ Tcells, associated with HTLV-1. Rash, lymphadenopathy, HSM, lytic bone lesions, hypercalcemia.
CML
mature myeloid cells, basophils are increased, t(9:22) BCR-ABL fusion, increased tyrosine kinase activity, tx: infliximab. If splenomegaly is getting worse, indicates progression towards acute leukemia (AML or ALL).
Polycythemia vera
mature myeloid cells, especially RBCs. JAK2 mutation, blurry vision, headache, venous thrombosis, flushed face, itching after bathing. Risk of Budd-Chiari. Tx: Phlebotomy, hydroxyurea. EPO is low and SaO2 is normal.
Essential Thrombocythemia
Mature myeloid, especially platelets, JAK2 mutation, risk of bleeding or thrombosis. Rarely progresses to leukemia, gout, or fibrosis.
Myelofibrosis
Mature myeloid, especially megakaryocytes. Makes extra PDGF which causes bone marrow fibrosis. Splenomegaly due to hematopoesis, leukoerythroblastic cells on smear (no reticulin gates), tear drop cells on smear. Risk of infection, thrombosis, and bleeding.
Rituximab
anti CD20+ useful in small B cell lymphoma
Nonhodgkin’s Lymphoma
Small cell types: Follicular, Mantle (cyclinD), Marginal (associated with Hashimoto’s thyroiditis, sjogren’s, and H pylori)
Intermediate Cell types: Burkitt Lymphoma associated with EBV, c-myc translocation, starry sky histology.
Diffuse Large Cell: most common NHL, clinically aggressive, can be from follicular lymphoma.
Hodgkin Lymphoma
Reed-Sternberg cells (CD15 and CD30+), Nodular Sclerosing is most common type, presents in young females, histology shows broad bands of fibrosis within the LN and lacunar cells (isolated Reed Sternberg cells)
