Leukemia and Immunology

What is the most common cause of spontaneous tumor lysis syndrome in leukemia?

High tumor burden outgrowing vascular supply → hypoxia → Na⁺/K⁺ ATPase failure → cell swells and eventually lysis

What are the hallmark metabolic derangements in tumor lysis syndrome?

Hyperkalemia, hyperphosphatemia, hypocalcemia, hyperuricemia, elevated LDH

Why does tumor lysis cause hyperkalemia?

Intracellular K⁺ is released from lysed tumor cells (bc of Na?K pump the cells have lots of K inside them)

Why does tumor lysis cause hyperphosphatemia?

Tumor cells are rich in phosphate from nucleotides and phospholipids

Why does tumor lysis cause hypocalcemia?

Phosphate binds calcium → calcium phosphate precipitation (Ca2+ sticks with phosphate and becomes calcium phosphate so less free Ca2+)

Why does tumor lysis cause hyperuricemia?

Cell lysis=>Nucleotide breakdown and spread → purines → xanthine → uric acid via xanthine oxidase

Why is LDH elevated in tumor lysis syndrome?

Tumor cells rely on glycolysis → LDH converts pyruvate to lactate to regenerate NAD⁺ for glycolysis (tumor cells hoard LDH)

What is the mechanism of urate nephropathy in Tumor Lysis Syndrome?

Uric acid precipitates in acidic renal tubules → obstructive nephropathy

What is the role of allopurinol in TLS?

Xanthine oxidase inhibitor → prevents new uric acid formation (but doesn’t reduce existing urate)

What is the role of rasburicase in TLS?

Recombinant urate oxidase → converts uric acid to allantoin (soluble)

What is the mechanism of hydroxyurea in Acute Myeloid Leukemia?

Inhibits ribonucleotide reductase → blocks dNTP synthesis → S-phase arrest and no DNA synthesis

What is the mechanism of cytarabine (Ara-C)? (C makes an S sound)

Cytidine analog → incorporated into DNA → chain termination during S-phase

Why is cytarabine given by continuous infusion?

To ensure exposure during S-phase, which varies across tumor cells

What is the mechanism of daunorubicin?

Intercalates DNA, inhibits topoisomerase II, generates free radicals → DNA damage (Think RUBs help me unwind)

What is the mechanism of midostaurin in FLT3-mutated AML?

Tyrosine kinase inhibitor → blocks ATP binding to FLT3 receptor → inhibits signaling

Brute memorization as of now

Why does high-dose cytarabine overcome resistance?

Overcomes downregulation of ENT1 (SLC29A1) by mass action

What is the first step in the innate immune response to bacteria?

Spontaneous hydrolysis of C3 → C3b binds bacterial surface (alternative pathway»sprinkles on icecream)

What stabilizes the C3 convertase on bacterial surfaces?

Properdin binds C3bBb complex

What is the function of C5 convertase?

Cleaves C5 → C5a (inflammatory) and C5b (initiates MAC)

What is the membrane attack complex (MAC)?

C5b + C6throughC9 → forms pore(drills a hole) in bacterial membrane → lysis (bacterial cell leaks out and dies (especially Neisseria)

What are the roles of C3a and C5a?

Anaphylatoxins → recruit and activate neutrophils, increase vascular permeability, inflammation

How does C3b enhance phagocytosis?

Opsonizes bacteria → binds CR1 on neutrophils/macrophages

What cytokine is produced by macrophages upon PRR activation?

IL-12

What does IL-12 do?

Activates NK cells → secrete IFN-γ → activates macrophages

What cytokines are secreted by activated macrophages? (think inflammation)

TNF-α, IL-1, IL-6, IL-12 → promote inflammation

What signals are required for CD4⁺ T cell activation?

TCR:MHC II + CD28:CD80/86 (costimulation)

What cytokine drives TH1 differentiation?

IL-12 (from DCs/macrophages) and IFN-γ (from NK cells)

What is the function of TH1 cells?

Secrete IFN-γ → activate macrophages to kill intracellular bacteria

How do B cells recognize bacterial antigens?

BCR binds antigen + CR2 binds C3d → strong activation

What is the role of Helper T cells?

Provide help to B cells in germinal centers → class switching and affinity maturation

How do antibodies enhance phagocytosis?

Fc receptors on phagocytes bind Fc region of IgG-coated bacteria

How does the classical complement pathway get activated?

C1q binds Fc region of antibody on bacteria → activates C3 convertase (Classic= C1 binds Fc of antiBody)

How does the Lectin pathway get activated

identifies sugars(ex: mannose); eventually forms C3 convertase

How does the alternative pathway get activated?

Spontaneous hydrolysis of C3»c3 convertase

CD19 is a marker for____. Low CD19 with normal CD3 incidates:

B-cells. Indicates X-linked agammaglobulinemia or Bruton’s/BTK where B cells are missing but T cells are normal

What histological feature is pathomneumonic to Acute Myeloid Leukemia

Auer Rod