Myeloproliferative Disorders Flashcards
3 types of myeloid neoplasms
- AML
- Myelodysplastic syndrome
- Myeloproliferative disorders
is characterized by blasts that replace bone marrow & suppress normal hematopoiesis.
AML
(myeloproliferative disorders are tumors that increase myeloid elements, ex: CML)
CML is a myeloproliferative disorders where myeloid tumors increase _____.
myeloid elements
In myeloid neoplasms, what are 2 factors that determine the type of disease (AML, myelodysplastic, or myeloproliferative)
- Hierarchical position of transformed cell (stem cell or further down lineage)
- effect of transforming event on differentiation
4 myeloproliferative disorders
- CML
- Polycythemia vera
- Essential thrombocytosis
- Primary myelofibrosis
Mutation in CML? Consequence?
- BCR-ABL fusion gene
- ABL kinase activation
Which 3 myeloproliferative disorders have a JAK2 point mutation (consequence = JAK2 kinase activation)?
- Polycythemia vera
- Essential thrombocythemia
- Primary myelofibrosis
(Or MPL point mutations → MPL kinase activation)
Mutation in Systemic Mastocytosis? Consequence?
KIT point mutation → KIT kinase activation
Mutation in Chronic eosinophilic leukemia? Consequence?
FIP1L1-PDGFRA fusion gene → PDGFRa kinase activation
Mutation in Stem cell leukemia? Consequence?
FGFR1 fusion gene → FGFR1 kinase activation
BCR-ABL (Philadelphia chromosome) is the cause of _______ (disease)
CML
(short chromosome 22)
In CML, constitutive activation of BCR-ABL → activation of which pathways (2)?
- RAS
- JAK-STAT
(leads to proliferation of granulocytic & megakaryocytic precursors → immature granulocytes in blood (bands))
Which myeloproliferative disorder is dx w/PCR or chromosome analysis?
CML
Which Myeloproliferative disorder has leukocytosis, blasts, and anemia
CML
CML typically affects which age group? Polycythemia Vera? Primary myelofibrosis?
- 50-60s
- Late middle age
- >60
CML is a neoplastic proliferation of myeloid precursors which would normally go on to become ______ (3).
- monocyte
- erythrocyte
- megakaryocyte
CML symptoms (3)
- splenomegaly (“dragging” sensation)
- weakness
- weight loss
(primary myelofibrosis also has splenomegaly)
______ exposure is a risk factor of CML
benzene
Which myeloproliferative disorders are treated with tyrosine kinase inhibitors and which are treated with phlebotomy?
TKI: all but polycythemia vera, which is treated with phlebotomy
Imatinib is a tyrosine kinase inhibitor that targets _______ protein.
BCR-ABL
(possible resistance mutation: T315l)
Goal of therapy w/Imatinib
- complete hematological response after 3 months
- complete cytogenic response after 6 months
(possible resistance if the mutation is T315I)
Panmyelosis, increased Hct and HTN indicates which myeloproliferative disorder?
Polycythemia vera
(panmyelosis = RBCs, granulocytes & platelets)
Polycythemia vera: sx (3)
- cyanosis (due to hyperoxygenation)
- bleeding
- thrombotic episodes
Essential thrombocytosis: sx (3)
dysfunctional platelets (thrombosis & hemorrhage)
(NO myelofibrosis (marrow fibrosis) or polycythemia vera (lack of panmyelosis)
Which myeloproliferative disorders has a very high lab value of platelets?
essential thrombocytosis
Primary myelofibrosis: sx (2)
- anemia
- splenomegaly (due to extramedullary hematopoiesis)
Early Primary Myelofibrosis labs will show _______ (2). Late? Very late?
- Leukocytosis & thrombocytosis
- Hypocellular & fibrotic marrow
- osteosclerosis
Which myeloproliferative disease is characterized by teardrop shaped RBCs (aka Dacrocytes) & nucleated RBCs on blood smear?
Primary myelofibrosis
