Chronic Myeloproliferative Disorders

Question 1

common characteristics of MPD (6)

Answer 1

increased numbers of cells from one or more cell lines
hepatosplenomegaly
clonal marrow expansion
hypercatabolism (fevers, sweats, weight loss)
can evolve into AML
loss of control of normal proliferation

Question 2

mutation that drives MPDs

Answer 2

JAK2 mutations –> constitutive activation of proliferation of RBCs, platelets, or neutrophils/monocytes

Question 3

chronic myeloid leukemia: s/sx

Answer 3

sx: fevers, chills, fatigue, weight loss, early satiety, abdominal pain
PE: splenomegaly

Question 4

chronic myeloid leukemia: labs (CBC, BMB, cytogenetics)

Answer 4

increased WBC - +/- elevated Hgb and platelets –> anemia and thrombocytopenia later in disease
increased LDH
Smear: immature myeloid cells, but few blasts
bone marrow biopsy: hypercellular marrow w/ increased myeloid: erythroid ratio
cytogenetics: t(9,22) = philadelphia chrom

Question 5

t(9,22)

Answer 5

BCR-Abl fusion protein –> constitutively active kinase –> promotes growth and prevents apoptosis

Question 6

CML tx

Answer 6

tyrosine kinase inhibitor - blocks BCR-Abl

• try two
• if these fail, consider HSCT

Question 7

polycythemia vera sx/s

Answer 7

sx: same as CML but w/ headache, visual disturbances, thromboisis, pruritus – hyperviscoisity sx
PE: splenomegaly, plethora, hepatomegaly

Question 8

polycythemia vera labs (CBC and molecular dx)

Answer 8

high Hgb/Hct
Peripheral smear normal
Erythropoietin LOW
molecular diagnostics: JAK2 mutation

Question 9

how to differentiate polycythemia vera from RBC increase in response to physiologic stress?

Answer 9

Splenomegaly in PV

Question 10

tx for polycythemia vera

Answer 10

tx not great

phlebotomy - remove excess RBCs and make pts iron deficient so they can’t make so many RBCs

Question 11

essential thrombocythemia s/sx

Answer 11

hyper viscosity things - headache, lightheadedness, syncope, visual changes

Question 12

dx of essential thrombocytopenia

Answer 12

high platelets
increased megakaryocytes in BM
mutation in JAK2 or MPL (same gene for myeloproliferative leukemia)

Question 13

tx for essential thrombocytopenia

Answer 13

low risk (<1000) - no tx
high risk - hydroxyurea

Question 14

primary myelofibrosis

Answer 14

same sx as CML
PE: splenomegaly
lab findings: anemia and teardrop red blood cells
BM: increased megakaryocytes, fibrosis/collagen in BM
tx: HSCT, HU, tranfusions, JAK2 kinase inhibitors maybe