CML Module 5/15/14 Flashcards
What sort of cells would you find in CML
Mature cells + left shift in neutrophil series but not a whole lot of blasts.
CML disorder of stem cells. Stem cell before myeloid/lymphoid progenitors even.
Chronic Myeloproliferative Disorders things you must know
- Malignant proliferation of myeloid cells (not blasts, but maturing cells) in blood, bone marrow
- Four disorders: CML, PV, ET, MF
- Occur only in adults***
- Long course
What is proliferating the most?
CML–neutrophils
PV–red cells
ET–platelets
MF–everything
Features common to all 4 disorders
- Occur only in adults***
- Long clinical course
- Increased WBC with left shift (not a huge left shift where you only see blasts. May see a couple.)
- Hypercellular marrow
- Big spleen (extra medullary hematopeoisis)
- May evolve into acute leukemia (can acquire additional genetic abnormalities)(when happens usually a terminal event)
- Mutated tyrosine kinases
CML things you must know
- Neutrophilic leukocytosis
- Basophilia
- Philadelphia chromosome
- Three phases
Laboratory findings in CML
- Dramatically increased WBC
- Neutrophilia with left shift
- Basophilia
- Decreased hemoglobin
- Increased platelet count (at first)
- Decreased LAP (neutrophil/leukocyte alkaline phosphatase)(enzyme present in neutrophils)(in CML malignant neutrophils they don’t make LAP).
CML genetics
t(9:22)
9 doesn’t really do mud.
New chromosome 22 you end up w/ hybrid gene that makes nasty/super active tyrosine kinase.
Clinical findings in CML
Symptoms
- slow onset
- fever, fatigue, night sweats
- abdominal fullness (dragging sensation d/t huge spleen)
Signs
- huge spleen
- big liver
- maybe some lymphadenopathy
Phases of CML
Chronic phase
- stable counts
- easily controlled
- 3-4 years (untreated)
Accelerated phase (50%)
- unstable counts
- blast crisis within 6-12 months
Blast crisis (50%)
- acute leukemia (ironically many get acute lymphoblastic leukemia because the initial pathogenetic problem happens in stem cell that hasn’t even decided myel v. lym progenitor series)
- high mortality
Remission
Hematologic remission
- no splenomegaly
- WBC <10,000, normal morphology
- normal HgB, platelet count
Cytogenetic remission
-no metaphases w/ t(9;22)
Molecular remission (most sensitive) -No BCR/ABL transcripts by PCR
Polycythemia Vera things you must know
High RBC (makes blood sludgy)
Different from secondary polycythemia
Thrombosis and hemorrhage
Jak-2 mutation
Polycythemia Vera general info
“Polycythemia”=increased red cell mass (other reasons exist for increased red cell besides PV such as living at high altitude etc)
Primary (intrinsic myeloid cell problem)
Secondary (d/t increased erythropoietin)
Diagnostic criteria for PV
A (major criteria) (A1 and A2 required but mixture of others)
A1 increased red cell mass
A2 normal O2 saturation
A3 splenogmegaly
B (minor) criteria
B1 thrombocytosis
B2 increased WBC w/o infection
B3 increased LAP (not a typo even though not the case in CML)
B4 increaed B12
Clinical findings in PV
Signs
- HA, pruritis (possibly d/t basophils), dizziness
- thrombosis (so many red cells around), infarction
Sx
- big spleen, liver
- plethora (red face)
JAK-2 in PV
Normal JAK-STAT pathway (don’t need second messenger)
- cell signaling pathway
- important in many different cell types
JAK-STAT in PV
- Mutated JAK-2: activity increased in PV (inhibited inhibitor)
- Cells grow on their own
-Important for diagnosis and drug therapy
