CML module

Question 1

CML primary cells that are proliferating

primary chromosome finding

Answer 1

neutrophils (also basophils!!)

philadelphia chromosome (9;21)

Question 2

PV

main points

Answer 2

polycythemia vera - predominantly malignant RBC

makes blood sludgy, thrombosis, hemorrhage

Jak-2 mutation (tyrosine kinase) - used for Dx - upregulated and cells grow like apeshit

Tx - phlebotomy

Question 3

ET

main points

Answer 3

essential thrombocythemia - predominantly malignant magakaryocytes/platelets

can occur in young women

Dx -
platelets >600k
Hgb

Question 4

MF

Answer 4

myelofibrosis - all myeloid cell lines are malignant

extramedullary hematopoiesis

tear drop red cells

SSx - huge, full feeling spleen, weakness, fatigue, tachycardia, pallor

Tx - supportive, median death 3-5 years

Question 5

what cell surface enzyme is constitutively on in all myelomas

Answer 5

tyrosine kinase - cell is always in growth mode and never in differentiation mode

Question 6

LAP test

Answer 6

if negative, you have cancer, tests for leukocyte alkaline phosphatase which cancer cells don’t bother to make

Question 7

one main drug that treats CML

Answer 7

imatinib - tyrosine kinase inhibitor - blocks ABL1 kinase by blocking ATP binding

Question 8

what genomic translation causes the defects seen in CML, more specific that philadelphia chromosome

Answer 8

BCR-ABL translocation creates BCR-ABL fusion protein - a constitutively active tyrosine kinase

Question 9

can BCR-ABL1 progenitor cells self renew?

Answer 9

NO, and they DO continue to differentiate - you get Expansion of progenitor and
committed cells, but mature cells are still produced. Disease is relatively mild.

this is the chronic phase of CML

Question 10

What protein drugs target EGFR and are signal transduction inhibitors

Answer 10

erlotinib gefitinib