Molecular Basis Of Hematologic Malignancy

Question 1

Polycythemia Vera (disease and mutation)

Answer 1

• erythrocytosis causing thick blood

- due to JAKV617F mutation causing constitutive myeloproliferation

Question 2

CML (mutation)

Answer 2

9;22 translocation (Philadelphia chromosome) causes BCR-cABL mutation, constitutively active tyrosine kinase, myeloproliferation

Question 3

Hairy Cell Leukemia (mutation)

Answer 3

-BRAF mutation (BRAF mutation also associated with MM and Langerhans Cell Histiocytosis)

Question 4

Burkett Lymphoma (disease, mutation)

Answer 4

• mature B-cell tumor (endemic = EBV, Africa, Sporadic = abdominal tumors)
• overexpression of c-MYC (regulates transcription and cell proliferation) due to t8;14

Question 5

DLBCL (disease + mutation)

Answer 5

• most common NHL

- BCL-6 overexpression (Bcl-6 represses cell response to stress, like p-53 and apoptosis)

Question 6

AML (disease + mutation)

Answer 6

Proliferation of immature myeloid progenitors in bone marrow, causing cytopenias
-Caused by t15;17, blocking RAR (retinoic acid receptor- normally binds E2F for proliferation)

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Question 7

Mantle Cell Lymphoma (disease, mutation)

Answer 7

Small B-cell lymphoma in mantle zone
-t(11;14) causes constitutive cyclin D1 expression, allowing uncontrolled G1/S transition in cell cycle (cyclin D1 phosphorylates Rb, releasing E2F to cause transcritption)

Question 8

Follicular Lymphoma (disease, mutation)

Answer 8

Small B-cell lymphoma of germinal centers
-due to t(14;18) translocation causing Bcl-2 overexpression (Bcl-2 binds pro-apoptotic Bax/Bak, preventing apoptosis. Normally Bid/Bad/PUMA bind up Bcl-2 to free Bax/back to cause apoptosis, but cant if Bcl-2 overexpressed)