Myeloproliferative disorders- P Flashcards
What is a myeloproliferative disorder?
Neoplastic proliferation of mature cells of myeloid linage
- age of onset 50-60
In Myeloproliferative disorder what happens to the bone marrow and white count?
Increased WBC
Hypercellular BM
What are some complications of myeloproliferative disorders?
- Increased Risk of hyperuricemia and gout due to high turn over a cells
- Progression of marrow fibrosis and transformation of acute leukemia
How would high cell turn over lead to hyperuricemia?
Degradation of Purines found in the nucleus of cells leads to increased uric acid in the blood
What is one high yield characteristic of CML?
Basophilia
What is the definition of CML?
Neoplastic proliferation of mature myeloid cells
- especially granulocytes and precursors
CML is driven by a translocation. What is it? how is it treated?
Philadelphia chromosome translation of 9 and 22
- Generated fusion between BCR-ABL which increase tyrosine kinase activity
- treated with TKI- Imatinib
What are the 3 phases of CML? How are they characterized?
- Chronic- splenomegaly
- Accelerated- enlarging spleen and phase 3 to follow shortly
- Transformation- acute leukemia
CML can transform into?
AML- 66%
ALL- 33%
CML needs to be distinguished from leukemoid reaction. How can one do this?
- Negative leukocyte alkaline phosphatase (LAP) stain in CML. Where the granulocytes in the leukemoid reaction need the LAP to fight infection. Neoplastic cells in CML do not.
- Increased basophils in CML
- 9–> 22 translocation in CML
What is Polycythemia Vera (PV)?
Neoplastic proliferation of mature myeloid cells
- especially RBC’s
- granulocytes and platelets also increased
What mutation is ass. with PV?
JAK 2 mutation
What are the clinical sx’s ass. with PV and why is this so?
Hyper-viscosity of Blood causes:
- Blurry vision and HA
- Increased risk of venous thrombosis
- Plethora
- Itching, especially after bath/shower due to histamine release
How would one go about treating PV?
Phlebotomy
- 2’ line treatment is hydroxyurea
- without treatment- death occurs in about 1 year
What is reactive polycythemia?
increased in cells for a reactive reason
- ex. you need more RBC’s because you have COPD and you traveled to Denver for the week. Thus you body will push out more EPO to make more RBC’s to be more efficient at getting O2 to your tissues
FYI- can be any cells
How does one distinguish between PV and reactive polycythemia and Renal Cell Carcinoma?
RCC- SaO2- Normal, EPO high (due to ectopic epo production)
PV- SaO2- Normal, EPO Low
RP- SaO2- Low, EPO high
What is Essential thrombocythemia (ET)?
Neoplastic proliferation of mature myeloid cells
- especially platelets
What mutation is ET ass. with?
JAK2 kinase mutation
What are the sx’s related to in ET?
Bleeding and thrombosis depending on the action of the platelets (non-functioning and overactive, respectively)
Can ET turn into a Acute leukemia or marrow fibrosis?
Rarely
- No significant risk of gout or hyperuricemia
Why doesnt ET create gout via hyperuricemia?
Because Platelets are made from Megakaryocytes. They are basically blebs off of the MK cells cytoplasm. No Nucleus to degrade to create these sx’s.
What is myelofibrosis?
Neoplastic proliferation of mature myeloid cells
- especially megakarycytes
In 50% of the cases which mutation is myelofibrosis ass. with?
JAK2 kinase mutation
What do factor does megakaryocytes produce that cause marrow fibrosis?
Platelet-derived growth factors (PDGF)
What are the clinical features of myelofibrosis?
- splenomegaly
- Leukoerythroblastic smear- tear drop RBC’s, Nucleated RBC’s and blasts granulocytes
- Increased risk for infection bleeding and thrombosis
How does myelofibrosis cause splenomegaly?
As the marrow becomes more fibrotic it can no longer do its job of hematopoiesis. Thus the body takes over and turns back the clock resorting in the spleen and liver for hematopoiesis as it did as a fetus.
