Myeloproliferative Neoplasms Flashcards
what are myeloproliferative neoplasms (MPNs)?
clonal haematopoietic stem cell disorders with an increased production of one or more types of haemopoietic cells
what do MPNs result in?
increased production of mature, differentiated cells
what are the two groups of MPNs?
BCR-ABL1 negative diseases
BCR-ABL1 positive diseases
name three BCR-ABL 1 MPNs?
polcythaemia vera
primary myelofibrosis
essential thrombocythaemia
name a BCR-ABL 1 positive MPN
chronic myeloid leukaemia
what happens in CML?
the proliferation of myeloid cells
how does CML present?
can be asymptomatic
splenomegaly
gout
hypermetabolic symptoms
what features are seen on the blood count in CML?
normal or reduced HB
leucocytosis with neutrophilia, eosinophilia and basophilia
thrombocytosis
what bone marrow change is seen in CML?
increased cellularity
what is the genetic hallmark of CML?
the philadelphia chromosome
what does the philadelphia chromosome result in?
formation of a new gene - BCR-ABL1
results in production of a tyrosine kinase with causes abnormal phosphorylation
what drugs can be given for CML?
tyrosine kinase inhibitors
name a tyrosine kinase inhibitor
imatinib
what are the features common to MPNs?
may be asymptomatic gout fatigue weight loss sweats splenomegaly thrombosis
what is erythromelalgia?
redness and pain in the hands and feet due to microvascular occlusion
what blood count changes are seen in polycythemia vera (PV)?
high Hb/haematocrit accompanied by erythrocytosis
what can cause secondary polcythaemia?
chronic hypoxia
what can causes pseudopolycythaemia?
dehydration
diuretic therapy
obesity
how does PV present?
headache
fatigue
aquagenic pruritus
what genetic mutation is seen in PV?
JAK2 mutations - seen in 95% of patients
what is the main aim of treatment for PV?
reduce thrombosis risk
how is PV managed?
venesect to haematocrit <0.45
aspirin
cytotoxic oral chemotherapy
what chemotherapy drug can be given for PV?
hydroxycarbamide
what happens in essential thrombocythaemia (ET)?
overproduction of platelets
what is there a risk of in ET?
thrombosis
what genetic mutations can be seen in ET?
JAK2
CALR
MPL
some patients are “triple negative” and have no mutations
what is the characteristic bone marrow appearance in ET?
increased amounts of abnormal looking megakaryocytes
how is ET managed?
aspirin
cytoreductive therapy to control proliferation
what drugs can be involved in the cytoreductive therapy in ET?
hydroxycarbamide
anagrelide
interferon alpha
how does primary myelofibrosis (PMF) present?
marrow failure
splenomegaly
hypercatabolism
what is seen on the blood film in PMF?
tear drop shaped RBC
leucoerythroblastic changes
what does leucoerythroblastic mean?
the presence of neutrophil and red cell precursors
what mutations can be seen in PMF?
JAK2
CALR
MPL
how is PMF managed?
supportive care
JAK2 inhibitors
allogenic stem cell transplant in very few patients
name a JAK2 inhibitor
ruxolitinib
