Negative Flashcards
> It is composed mainly of 3 specific disorders: ______,______,______
between_______ years of age.
> increase in one or more myeloid cells lines (platelets, erythrocytes, myelocytes): morphologically and functionally normal
53 and 64
ET, PV, and primary myelofibrosis (PMF).
- initially presents with a leukocytosis and a left shift
- slowly develops fibrosis in the bone marrow that inhibits hematopolesis - eventually
resulting in pancytopenia
PMF
- must present with erythrocytosis but also shows leukocytosis
PV
- thrombocytosis but can also exhibit leukocytosis and a left shift
ET
MOLECULAR PATHOPHYSIOLOGY: ET, PV, PMF
• share three common gain-of-function driver mutations:
JAK2 (JAK2 V617F)
calreticulin (CALR)
myeloproliferative leukemia virus oncogene (MPL) “thrombopoietin receptor” (TPOR)
- has 7 domains (JH1 through JH7): two domains (JH1 and JH2) control the kinase activity.
JAK2 protein
- closely associated with cytokine receptors EPO, TPO, and G-CSF
- controls transphosphorylation through conformational inhibition
JAK2 protein
- is a tyrosine kinase enzyme much like the ABL1 moiety of the BCR::ABL1 fusion gene found in CML
JAK2 protein
cytokine receptor binds its ligand > activates_____ protein (transphosphorylation) - bound to the cytoplasmic region of the receptor
JAK2
- the most common JAK2 mutation
- 95% of patients with PV and is found on chromosome band_____.
JAK2 V617F
9p24
•mutated ________ - activation of several signal transduction pathways that are (normally activated after EPO stimulation)
Mutated_____ is active and will phosphorylate STAT proteins in the absence of erythropoietin or will over phosphorylate in its presence
mutated JAK2 protein
JAK2
DISEASE PROGRESSION
•_____ - progress to PV
• either_____ - to sMF
ET
ET or PV
• - lesser role in disease progression
driver mutations (JAK2, MPL, and CALR)
• - greater risk of leukemic transformation than PV patients with a high JAK2 allele burden.
triple-negative PV patients (negative for JAK2, MPL, and CALR)
