3.25.14* Myeloproliferative Disorders Flashcards
PPT* Lecture Notes* Reading (pp. 192-213)* Pictures
hematologic malignancy
a. there is too much of stuff-unregulated growth or two little apoptosis
b. maturation arrest-
*Mechanism of action of JAK-2 V617F mutation
constitutive activation of Epo receptor leads to
*Diagnostic criteria for P Vera
a. JAK-2 V617Fn (95%)
b. Hgb over 18.5 in men and 16.5 in women or other evidence of increased red cell volume
*Diagnostic criteria for ET
a. 50-60 y/o
b. high platelets (and WBC)
c. Jak2V617F
d. causes thrombotic occlusions called erythromelalgia.
e. PBS: giant platelets
*Diagnostic criteria for primary myelofibrosis
a. hepatosplenomegaly, anemia, leukocytosis, thrombocytosis
b. PBS- nucleated RBC, giant platelets, teardrop RBCS, left shift
c. reticulin or collagen fibrosis
d. treatment: Jak2 inhibitor, BMT
*Diagnostic criteria for chronic myeloid leukemia
a. hepatosplenomegaly, over 60
b. PBS: elevated EBC, platelets, basophilia. All stages of granulocyte differentiation (look like HSV).
c. bone marrow: hypercellularity, increased ratio of myeloid cells to erythroid cells, increased megs.
*three causes of secondary polycythemia
chronic hypoxia (sleep apnea)
Epo secreting tumors
high affinity hemoglobin
*treatment of P vera
a. phlebotomy
b. aspirin (to reduce thrombosis)
c. hydroxyurea (to reduce thrombosis)
d. interferon (reverses increased platelets/WBC and splenomegaly)
e. JAK2 inhibitor
*mutation in mastocytosis
c-KIT leading to mast cell activation/proliferation
*mutation in chronic eosinophilic leukemia
PDGFRA
*organs damaged in eosinophilia
heart lung GI thromboses eczema
*causes of secondary eosinophilia
drug hypersensitivity, infection, hypoadrenalism, and solid organ neoplasm
*Mutation and mechanism of action of Philadelphia chromosome
BCR-ABL in CML causing constitutive tyrosine kinase activaiton
- Mechanism of action of present best therapy for CML
tyrosine kinase inhibitor (imatinib)
*Peripheral blood picture in CML
Looks like bone marrow without megakaroyctes because of so many white cells in the blood. Usually just bands and segs, but when you see blasts, myelocyte, promyelocyte in the peripheral blood there is something wrong if you don’t have sepsis.
The MPN category includes
chronic myelogenous leukemia (CML) polycythemia vera (PV) essential thrombocythemia (ET) primary myelofibrosis (PMF) chronic neutrophilic leukemia (CNL) chronic eosinophilic leukemia Systemic mastocytosis (SM)
Which does not belong when explaining myeloproliferative neoplasms? Myeloid accumulation Clonal Stem cell mutations Full maturation Dysplastic differentiation
(there is a myeloid differentiation, the mutation is all the way back in the stem cells)
Symptoms of polycythemia vera
itch (due to histamine release)
headaches
fatigue
Signs of polycythemia vera
plethora
splenomegaly
conjunctival plethora
what is the main cause of death in patients with PV
thrombosis
acute myeloid leukemia
What is seen in PBS of P vera
often hypochromic microcytic due to iron deficiency (from GI bleeding)
Elevated RBC, WBC and platelets
What is seen in bone marrow of P vera
hypercellular
loose clusters of pleomorphic megakaryocyttes
What happens in PV, post-polycythemia phase
marrow fibrosis
polycythemia vera
a. panmyelosis that is monoclonal
b. often mild
What is the difference between PV and ET
red cell mass
both have increased platelets and are Jak2 positive
ET therapy
a. hydroxyurea (reduced platelet count)
b. anagrelide (decrease platelets)
c. aspirin
patient has massive reticulin deposition in bone marrow
gonna need a bone marrow transplant
what is seen in mastocytosis?
a. urticaria pigmentosis- small itchy rash due to mast cell release
treatment for mastocytosis
a. prophylaxis to block mast cell mediators
b. interferon plus corticosteroids
treatment for CML
imatinib
allogenic transplants
