14. Chronic Myeloproliferative Neoplasms Flashcards
what characterizes the myeloproliferative disorders?
- somewhat like cancer: start from one mutated cell and have clonal proliferation
- hepatosplenomegaly
- CLONAL marrow expansion
- hypercatabolism (fevers, night sweats, wt loss)
- can evolve into AML
- loss of response to normal growth controls
chronic myeloid leukemia: what cell type is increased?
granulocytes
polycythemia vera: what cell type is increased?
RBCs
essential thrombocytosis: what cell type is increased?
platelets
idiopathic myelofibrosis: what cell type is increased?
granulocytes
what is a common mutation of RBCs that leads to polycythemia vera?
JAK2, tyrosine kinase
what is a common mutation of platelets that leads to essential thrombocythaemia?
JAK2, MPL kinase
what is a common mutation of neutrophils that leads to chronic myeloid leukemia?
BCR-ABL
what is a common mutation of monocytes that leads to idiopathic myelofibrosis?
JAK2, MPL
what mutation is responsible for most of polycythemia vera, half of essential thrombocytheamia, and half of myelofibrosis?
JAK2
for normal functioning, how is hematopoiesis stimulated? how does this change with a mutation?
normally cytokines bind to surface receptors, which activate transcription factors and incr gene transcription. with mutations (specifically to JAK2) this process is always turned on even if ligand is not present.
chronic myeloid leukemia: symptoms?
fevers, chills, sweats, fatigue, wt loss, early satiety (due to splenomegaly), abd pain
chronic myeloid leukemia: physical exam?
splenomegaly: may extend down into pelvis
chronic myeloid leukemia: labs results for WBC, Hgb, platelets, LDH
WBC high
Hgb may be high
platelets may be high
LDH high: good marker
chronic myeloid leukemia: peripheral smear?
immature myeloid cells (entire progression of WBCs: Pro-myelocyte ->myelocyte ->band ->PMN) but few blasts.
chronic myeloid leukemia: bone marrow biopsy appearance?
hypercellular marrow with incr myeloid:erythroid ratio
chronic myeloid leukemia: cytogenetics?
translocation between 9 and 22
chronic myeloid leukemia: Key to diagnosis?
cytogenetics: translocation between 9 and 22
chronic myeloid leukemia: appearance of peripheral smear that distinguishes it from AML?
CML: immature WBC forms but not many blasts
AML will have more blasts.
AML: why lots of blasts and then decreased downstream myeloid differentiation?
have expansion of blasts but then there is a differentiation BLOCK so the rest of cells in the lineage are decreased. see greater than 20% blasts.
what part of the cell count is up for both CML and AML?
total WBC is increased for both
