Myeloproliferative Neoplasms (MPNs) Flashcards
MPNs
monoclonal hyperprolifferation abnormalities (neoplasms) or myeloproliferative neoplasms.
What are the four types of MPNs?
- PV
- CML
- ET
- PMF (primary myelofibrosis)
Polycythemia Vera
unregulated proliferation of BM erythroid, granulocytic & megakaryocytes
PV Etiology
- gene mutation JAK2
-even though hyperactivity of JAK2 may not initiate PV, it is associated
JAK2 gene
nonreceptor tyrosine kinase that plays a role in EPO and TPO receptors
PV diagnosis
-2 major and 1 minor criteria must be met.
2 major criteria
- Hgb 18.5 M; 16.5F
- ID of JAK2 mutation
1 minor criteria
- panmyelosis in BM
- low EPO
- autonomous, erythroid
PV clinical symptoms
- Ruddy face
- itchy skin
- HTN
- vertigo
- feeling full
-blurred VA
-↑uric acid
-splenomegaly
-↑B12 serum - ↓Fe storage or absent
Lab findings
- RBCt=6-10x10^6/uL- severe crowding
-difficult pB smear - Hgb>18
- Hct=55-60%
-ESR =0-3mm/hr
-n or ↑WBC & plts w/ n. morph
-immature granulocytes - plts=400,000 to 2 mil
-BM hypercellular w/worsening fibrosis - ↓FE stable to spent phase
-nRBC
PV Tx’t
no cure, therapeutic phlebotomy 1st choice, myelosupressive drugs: ↓BV & ↑Fe stores.
Explain the etiology of Chromic Myelocytic Leukemia
an extreme elevation of mature/immature myeloid cells in BM which then show up in the p.B.
-This arises from a single translocation putting c-ABL next to BCR yielding BCR/ABL.
-BCR/ABL=↑ tyrosine kinase activity leading to hyperproliferation + unstable.
What are the lab findings in CML
- “when pB looks like B.M.”
- remember extreme elevation so >100,000/uL & usually 200,000-500,000/uL w/ neutrophilia, basophilia, & eosinophilia
- p.B has huge shift to the left w/ all developmental stages
- > 20% basophilia comes before blast crisis
- Abnormal cytogenetics
- M:E ratio 10:1-50:1 but when blasts are <30%
- ↑ plts or ↓ (>700,000 or <150,000/uL
What are the diagnostic testing for CML?
- karyotyping (chromosomal)
-FISH (cellular level) - PCR (molecular level)
-LAP decreased in early stages - BM shows striking increase in M:E ratio ranging from 10:1 to 50:1
Differentiate between the three phases of CML
- Chronic
- Accelerated: poor response to therapies and increased symptoms
- Blastic: 3/4 of pts undergo “blast transformation”. Blast >20% which can then indicate turning into either AML or ALL (rare).
*blastic phase involves pB, BM, & extramedullary tissues
What is treatment for CML & under what circumstances?
- primarily tx’t involved BMT for pts in chronic stage.
-Now Gleevec (imatinib mesylate) which binds to BCR/ABL causes a decrease in # GF receptors. This leads to abn. cell to die and increase in normal cell proliferation. - molecular remission observed
-“cures” 88% in chronic
What is the etiology of Primary Myelofibrosis (PMF)?
hematopoetic stem cell disorder of JAK2 in 65% of pts leading to hyperproliferation of BM fibrosis. Fibrosis occurs in response to neoplastic mutation elswhere causing an increase of GF. Can convert to AML
What are the clinical symptoms of PMF?
- SEVERE hepatosplenomegaly
- abdominal pain
- normo normo due to myeopthisic anemia
What are the lab findings in PMF?
- striking pB w/ aniso/poik w/ teardrops/dacrocytes
-poik becomes more severe as dz progresses to BM failure - left shift & ↑WBC count 15-30,000 /uL
- DRY TAP due to bone marrow fibrosis
-fibrosis does not allow proliferation of cells
What is the treatment of PMF?
-chemo
-steroids
-splenectomy
- eventual BMT
-pts usually die from 2 complications: overwhelming infections or massive hemorrhage.
What is the etiology of Essential thrombocytothemia?
HSC disorder with extreme increased megakaryopoiesis
-plt count ↑>600,000/uL
-plt fxn is abnormal unless plateletpheresis performed to reduce plt ct leaving plt crowding
What are clinical symptoms of ET?
- abdominal pain, epistaxis due to abnormal plts fxn, GI bleeding, & bleeding after minor dental sx
What are lab findings in ET?
600,000-2.5mil/uL
-giant / bizarre plts
-no nRBC
- slt left shift
- no megK fragments
What are the difference between ET and M7?
ET has +giant plts, noNRBC, slt left shift, no megK fragments.
M7 has giant plts, +nRBC, rare left shift, +megK fragm.
What are ET treatments?
Myelosuppressive drugs
-IFN-α if myelosuppressive drubs cannot be given
- plt apheresis to reduce plt mass
What peripheral blood abnormalities does CNL have?
elevated neutrophil count 80%>
What BM abn does CNL have?
hypercellular, dysplasia and fibrosis usually not present
What possible genetic abnormalities does CNL have?
- CSF3RT618I or other activating CSF3R
What pB abn does CEL have?
WBC>30%
What BM abd does CEL have?
-fibrosis is common, increased eosinophils
