Heme/onc Step 1

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Translocation 14;18 in most of these lymphomas

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Follicular lymphoma

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Translocation t(8;14), activation of C-myc oncogene, starry sky appearance

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Burkitt lymphoma

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HTLV-1

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Adult T cell lymphoma

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Mycosis fungoides - what is this and what can it progress to?

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Cutanoues T cell lymphoma that can progress to sezary syndrome

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Long term celiac disease can cause this lymphoma

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intestinal T cell lymphoma

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PAS+ leukemia, in children, very good prognosis

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ALL

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Auer Rods

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AML. Stain positive for myeloperoxidase. If APL - treat with all trans retinoic acid

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Acute leukemia shows a ton of ____ in marrow

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Blasts (either myeloblasts or lymphoblasts)

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Chronic leukemia doesn't have a lto of blasts (<5 % blasts). Instead, myeloid (CML) or lymphoid mature cells (CLL)

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just know that

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Smudge cells in this leukemia of elderly

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CLL

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Philadelphia chromosome (9;22) always present

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CML

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Pelger Huet Anomaly

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Cells that have two little lobes that look like sunglasses. Found in Myelodysplastic Syndrome - can progress to AML

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What are the myeloproliferative disorders? What mutation do they have in common?

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Polycythemia vera, Essential thrombocytosis, myelofibrosis

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JAK2 is a NON receptor tyrosine kinase

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just know that

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Pruirits after hot shower, splenomegaly, hyperviscous blood, and low erythropoietin

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Polycythemia vera

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Bone marrow with fibrosis infiltrate and teardrop shaped cells? Bone marrow for adipocyte infiltrate?

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Fibrosis - myelofibrosis. Fats - aplastic anemia

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Malignancy of plasma cells

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Multiple myeloma

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Anemia, renal insufficiency, back pain, hypercalcemia

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Multiple myeloma

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Bence Jones proteins in urine

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Immunoglobulin light chains in urine found with multiple myeloma

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Monoclonal antibody spike (M spike) on serum protein electrophoresis

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Multiple myeloma (remember, this is a plasma cell cancer making a ton of immunoglobulins, but makes just one type over and over, giving you that spike appearance)

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Rouleaux formation

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multiple myeloma - RBCs stacked like coins

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Multiple myeloma without bone lesions? monoclonal proliferation of IgM

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Waldenstrom macroglobulinemia

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MGUS

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Monoclonal Gammopathy of Undetermiend significance - proliferation of plasma cells but no myeloma symptoms, but CAN progress to multiple myeloma

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Solid tumor of plasma cells - can be solitary in bone or extramedullary in nose, and do not cause bone lesions

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Plasmacytoma

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Which 4 cancers have psammoma bodies?

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Papillary thyroid cancer, serous papillary cystandenocarcinoma of the ovary, meningioma, malignat mesothelioma

Front 26

Which cancers commonly metastasize to liver?

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Cancer Sometimes Penetrates Benign Liver - Colon, stomach, pancreas, breast, Lung

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How does methotrexate work to prevent thymidine synthesis?

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It's an analog of folic acid that inhibits dihydrofolate reductase

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What can you give with methotrexate to prevent myelosupression? What are other side effects of methotrexate?

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Leucovorin (aka folinic acid). Fibrotic lung disease and teratrogenicity are other side effects

Front 29

5 fluorouracil also inhibits pyramidine synthesis like methotrexate, but inhibits this enzyme instead

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Thymidylate synthase - can't convert dUMP to dTMP

Front 30

Leucovorin can't be used to treat myelosuppression you get with 5-fluorouracil - what can you use instead?

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Uridine

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Methotrexate, 5 Fluorouracil, and hydroxyurea inhibit ____ synthesis. 6 mercaptopurine and mycophenolate inhibit ____ synthesis

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Pyrimidine, Purine

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Toxicity of 6-mercaptopurine increases when patient is on

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Allopurinol, because it inhibits xanthine oxidase, which metabolizes 6-mercaptopurine

Front 33

Cytarabine is pyrimidine analog - how does it work?

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Inhibits DNA polymerase

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How does cyclophosphamide work?

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it's an alkylating agent - attaches an alkyl group to DNA, forming crosslink strands so DNA can't replicate

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Which side effect can cyclophosphamide cause? This is due to its toxic metabolite acrolein. You can prevent this by giving mesna with cyclophosphamide

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cystitis

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These anthracyclines are used to treat cancer

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Doxorubicin and daunorubicin

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How do doxorubicin and daunorubicin work?

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Generate free radicals and intercalate DNA

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What side effect is very important to know about doxorubicin and daunorubicin?

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Dilated cardiomyopathy because of free radical damage (heart cells have deficiency of superoxide dismutase)

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Bleomycin also generates free radicals - what side effect does this have?

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Pulmonary fibrosis - bisulfan and methotrexate also causes pulmonary fibrosis

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Cisplatin and carboplatin cross link DNA. They can cause nephrotoxicity and ototoxicity. Which other drugs also have these side effects?

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Loop diuretics! So do aminoglycosides vand vanco

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Fluroquinolones (eg ciprofloxacin) and etoposide both inhibit

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topoisomerase II

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Pilocytic astrocytoma and medulloblastoma are the two most common brain tumors in children. You can differentiate them on imaging - how?

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neurotoxicity, peripheral neuritis

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Vinblastine and vincristine block microtubule polymerization. Paclitaxel also works on microtubules but has a different mechanism of action

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They hyperstabalize microtubules so cells can't break down the microtubules to properly divide

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Tamoxifen is an estrogen receptor antagonist in ____ but agonist in ___

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breast, bone. It's a partial agonist in endometrium

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Tamoxifen increases your risk of

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endometrial cancer - because it's a partial agonist here. So it can be helpful in women who have endometrial cancer, but increases risk of endometrial cancer in women who DONT have it

Front 46

Monoclonal antibody against HER-2 used to treat breast cancers that express HER-2

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Trastuzumab

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Antibody against CD20, used to treat lymphomas, leukemias, and sometimes rheumatoid arthritis

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Rituximab

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tPA and other fibrinolytics can cause

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Reperfusion arrhythmias on arterial reopening due to rapid reperfusion (these are usually benign)

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What does c-myc actually do?

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it's a transcription activator

Front 50

Which chemotherapy drugs can cause nephrotoxicity, and what do you give to patients to minimize/prevent nephrotoxicity?

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Cisplatin - give amifostine (cytoprotective free radical agent) and hydration

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What do you give to prevent doxorubicin induced cardiotoxcicity?

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Dexrazoxane - iron chelating agent

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Angiogenesis is stimulated by these two growth factors

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VEGF and FGF (NOT EGF - epidermal growth factor)

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T(15;17)

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APL - acute promyelocytic anemia, subtype of AML. Auer rods. ATRA treatment

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What is the MDR1 gene and what does it code for?

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It codes for P glycoproteink, an ATP dependent efflux pump that pumps drugs out of cells and induces resistance to chemo drugs

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Hemorrhagic cystitis - side effect of which chemo drug and how can it be prevented?

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Cyclophosphamide. Give mesna (binds

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Malaise, anorexia, anemia, weight loss and generalized wasting

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Cachexia - caused by TNF-alpha

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Pulmonary fibrosis and skin discoloration are side effects of this chemo drug

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Bleomycin

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How does heparin work?

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Increases antithrombin activity

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What are the encapsulated bacteria that infect asplenic patients and what symptoms do they cause?

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Strep pneumoniae and H flu (pneumonias). Neisseiria meningitidis (meningitis), Salmonella (osteomyelitis), Klebsiella, E coli and Staph aureus also all can cause osteomyelitis

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Decreased warfarin efficacy with

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CP450 inducers

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Patients with renal dysfunction (eg diabetics) can have excessive bleeding due to accumulation of uremic toxins in the blood. this causes a QUALITATIVE platelet disorder - what would you see on PTT, PT, paltelet count, and bleeding time?

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everything normal besides bleeding time

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What is a hemarthrosis?

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Bleeding into joints - common in hemophilia

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Findings in DIC

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Prolonged PTT, PT. Thrombocytopenia/microangiopathic hemolytic anemia. Low fibrinogen. Elevated D dimer, Low factor 5 and 8.

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How do you monitor/early identification of DIC?

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Fibrinogen levels

Front 65

This protein is a regulator of G1 to S phase transition

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Retinoblastoma - Rb

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Increased incidence of Burkitt lymphoma and nasopharyngeal carcinoma

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EBV or mycoplasma, as well as CLL

Front 67

Neoplastic cells in multiple myeloma secrete

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IL-1 and IL-6 - activate osteoclasts and causes bone resorption/hypercalcemia.

Front 68

Amyloidosis and subsequent renal failure with this leukemia

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Multiple myeloma - renal failure due to plasa cell infiltration and deposition of amyloid

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Patients who recieve more than one body blood volume of whole blood or packed RBCs over 24 hour period can have elevated blood levels of ____. This can chelate calcium/magnesium and cause paresthesias

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Citrate

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Person over 50 with iron deficiency anemia - what do you have to rule out?

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Blood loss, especially from GI tract due to colon cancer

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Which antiretroviral drugs do not require activation via intracellular phosphorylation?

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NNRTIs - Neviparine, Efavirenz, Delaviridine

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These two drugs are HIV fusion inhibitors

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Enfuviritide (GP41), and Maraviroc (CCR-5)

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Integrase inhibitor (HIV drug)

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Reltegravir

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What are the protease inhibitors used to treat HIV?

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____navir (just know that) - prevent maturation and assembly of the virus.

Front 75

What are common side effects associated with NNRTIs?

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Hepatic failure with encephalopathy - flu like, abdominal pain, jaundice, fever

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15% of oral radiolabeled B12 is excreted in the urine (normal > 5) - is this pernicous anemia or dietary deficiency of B12 if this person has anemia?

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Dietary deficiency

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Which drugs can cause G6PD flare ups?

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Dapsone, antimalarial drugs, and TMP SMX

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Blurry vision due to increased VEGF

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Wet macular degeneration - angiogenesis due to elevated VEGF. Treat with anti VEGF therapy (ranibizumab)

Front 79

This is the drug of choice for hairy cell leukemia. It is resistant to degradation by adeosine deaminiase

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Cladribine - purine analog of adenosine

Front 80

Hepatitis B can integrate into DNA but hep C can't because it's an RNA virus

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just know this

Front 81

Waxing and waning lymphadenopathy with T(14,18) and BCL-2 oncogene overexpression

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Follicular lymphoma - most common indolent non hodgkin lymphoma in adults

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direct factor Xa inhibitors increase PT and PTT but not

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thrombin time

Front 83

integrin mediated adhesion of cells to basement membrane and extracellular matrix involves integrins binding to

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fibronectin, collagen, laminin

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BCL-2 is an oncogene because

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it has anti apoptosis effects

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Argatroban mechanism of action

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direct thrombin inhibitor - binds to thrombin active sites

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Abciximab blocks this receptor

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GP IIb/IIIa

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Treating B12 deficiency with folate can actually

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worsen neurological defects

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What is Li Fraumeni syndrome? What mutation is it associated with

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P53 mutation - autosomal dominant. Predisposes you to a ton of cancers (sarcomas, tumors of breast, brain, adrenal cortex)

Front 89

Pilocytic astrocytoma and medulloblastoma are the two most common cerebellar tumors in children. You can differentiate them on imaging - how?

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Pilocytic will have solid and cystic features (black and white), where meduloblastoma will just be solid (black)

Front 90

Ependymomas present with

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Bad headache, paiplledema, vomitting, HYDROCEPHALUS - obstruct CSF flow

Front 91

Hemosiderin accumulation in patients with hemolytic anemia or thalassemia b/c these patients often require frequent blood transfusions

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Just know that

Front 92

Down sindryome patients more likely to have this leukemia

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ALL

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extramedullary hematopoiesis can cause skeletal abnormalities and liver/spleen growth

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Thin bony cortex, impaired bone growth and deformities as well as hepatosplenomegaly

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This selective COX 2 inhibitor has anti-inflammatory effects without bleeding/GI side effects associated with nonselective ones

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Celecoxib

Front 95

Gram negative bacterial sepsis can cause

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DIC --> can cause schistocytes

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Which RBC fragmentation would you see with DIC?

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Schistocytes b/c this would be microangiopathic hemolytic anemia

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Pure red cell aplasia is associated with

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Thymoma (thymic tumor) and parvovirus B19

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ALL is the most common malignancy in children. Can be B cell or T cell ALL. T cell ALL often presents as a mediastinal mass and causes

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respiratory symptoms, dysphagia, or superior vena cava syndrome (compresses great vessels)

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Triad of acute renal failure, thrombocytopenia (prolonged bleeding time), and microangiopathic hemolytic anemia

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Hemolytic uremic syndrome (HUS) - often affects young children and associated with bloody diarrhea/shiga toxin

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Black pigmented gallstones common with

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chronic hemolytic anemia

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Rb, BRCA, P53, and APC are all anti oncogenes, that when mutated, can lead to cancer. K-ras rather is a

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proto oncogene

Front 102

Majority of nonselective NSAIDs have reverisble effects on cox. Aspirin has

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Irreversible effects on COX1 and2

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Side effects of ganciclovir and zidovudine HIV drugs?

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Neutropenia and bone marrow supression

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ERB-B2 positive breast cancer

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Another name for Her2/neu). Indicates aggressive tumor that can respond to trastuzumab

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Prognosis of a tumor is directly related to the STAGE (eg invasion/penetration to nearby tissues) rather than grade (differentiation)

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Just know that