CML PT2 Flashcards
- clonal expansion resulting to an increase in one or more myeloid cells
- lack the philadelphia chromosome
bcr;;abl1 negative
erythrocytosis but also shows leukocytosis and thrombocytosis
polycythemia vera
thrombocytosis but can also exhibit leukocytosis with a left shift
essential thrombocytopenia
t/f: bcr;;abl1 gene affects a single lineage
false - there might be a tri-lineage proliferation
- initially leukocytosis with a left shift but can also exhibit thrombocytosis
- slowly develops fibrosis that inhibits hematopoiesis —> pancytopenia
primary myelofibrosis
this mutation is necessary in stimulating proliferation and quesence
mpl
common mutations in bcr;;abl1 gene
mpl
jakk2v617f
calr
common feature among the 3 conditions
thrombocytosis
very common mpn
polycythemia vera
- mild erythrocytosis
- often asymptomatic and detected incidentally
prodromal phase
- proliferative phase
- hyperviscosity symptoms, thrombotic and hemorrhagic episodes
- splenomegaly, pruritus, erythromelalgia
overt polycythemic phase
- progressive splenomegaly or hypersplenism and pancytopenia
- post polycythemic myeloid metaplasia –> bone marrow fibrosis, anemia with tear drop cells
spent phase
increase in the actual number of rbc, wbc, and plt resulting from increase in production
true pancytosis
what mutation is notable in pcv
jak2v617f
pcv
- initial manifestation of pv
- independent of normal regulatory mechanisms associated with increased red cell mass
proliferative phase
only happens in post polycythemic phase
increase reticulin production
bone marrow with increased production in all blood cells
panmyelosis
in jak2 they control the kinase activity
JH1 and JH2
has the kinase activity
jh1
does not have kinase activity
jh2
what jh happens the dimerization of epo
jh2 and jh3
what will happen if jak2 is activated
it induces phosphorylation of stat proteins
- facilitated by jak2 –> stat protein
- causes a gene signal for gene expression to promote proliferation, differentiation, maturation, and inhibition of apoptosis
phosphorylation
valine is released in what domain and converts enzyme to its active form
jh2 domain
- confirmational change
- ducking point, point of dimerization
jak2
rare in pcv
jak2 exon12
jak2 exon12 is found in what mpn
secondary myelofibrosis
high epo levels, no jak2 mutation
secondary polycythemia
- normal rbc mass, predominant thrombocytosis
- jak2 mutation present, but lacks significant erythrocytosis
essential thrombocytopenia
- bcr-abl fusion gene
- leukocytosis with left shift, basophilia, splenomegaly
chronic myeloid leukemia
- prominent bone marrow fibrosis
- leukoerythroblastic reaction in pb
primary myelofibrosis
goal of theraphy for pcv
reduce hyperviscosity
treatment of choice for low risk patients in pcv
therapeutic phlebotomy
treatment for high risk px (young px or women in childbearing age)
pegylated ifn-a
- jak2 inhibitor
- first line of choice following hydroxyurea intolerance of failure
ruxolitinib
- epigenetic modifier
- induces apoptosis in neoplastic cells
givinostat
clonal mpn:
- increased megakaryopoiesis
- sustained thrombocytosis
essential thrombocythemia
drivers of acute anemia
alkylating agents
- if the clot remains attached to the blood vessel
- common due to thrombocytosis
- problem in sustained increase plt count
vascular occlusion or hemorrhage
- common in fingers and toes
- triggered when exposed to cold temp. or stress
- due to spasms in toes or fingers
reynaud syndrome and gout
common cause of death in essential thrombocythemia
bleeding and thrombosis
clonal mpn:
- increased abnormal megakeryocytes and granulocyte
- ineffective hematopoiesis with leukoerythroblastosis
primary myelofibrosis
serves as a matrix for structural framework in BM
collagen
the process by which the BM is replaced with connective tissue causing fibrosis
myelofibrosis
responsible for the production of collagen
fibroblast
what stain is used in reticulin fibers
gomori stain
cd marker for hsc and helps strongly in myelofibrosis
cd34+
- takes a sample of the bm
- examine the bm architecture, fibrosis, cellularity, etc.
bone marrow biopsy
- takes a sample of bone marrow fluid
- used to analyze individual cells
bone marrow aspiration
t/f: first line of theraphy in pm works
false
most common cause of death in PM
leukemic transformation
most common serious infectious agents in CNL
mycobacteria and fungi
only curative treatment inCNL
allogenic stem cell transplantation
