Module 1: Heme: CML and PM Flashcards
One of the last Leukemias to be discussed is Chronic Myeloid Leukemia. What is the pathogenesis for this?
malignant tumor of relatively mature granulocytes, resulting in proliferation
–basophils, neutrophils, metamyelocytes, myelocytes and eosinophils
–t(9;22): BCR-ABL — overactivity of TK receptor
White cell cancer of granulocytes so neutrophils, basophils, band cells, eosinophils and metamyelocytes take over the bone marrow.
what do you see on Bone Marrow biopsy for these patients?
Bone Marrow:
- -not pancytopenia (normochromic normocytic anemia) due to lack of neutropenia (the neutrophils are just malignant so thats why you get anemia with lots of neutrophils). Low Lap score = recurrent infections because neutrophils are malignant
- –Increased Total WBC count (lots of granulocytes and band cells)
- -increased band cells = bandemia = left shift = increased risk of developing blast crisis
- -Mimic Leukomoid reaction (but normal leukomoid reaction has increased LAP score)
What do you see on PB smear in CML?
PB smear:
-PMNs, basophils, eosinophils and blast cells and band cells
What is seen on BM aspirate in CML?
less than 10% lymphoblasts
–if converts to AML — blast crisis — greater than 20% blasts
What is the most accurate test for CML?
FISH
- -looking for t(9;22) Philadelphia chromosome
- -overactivation of the tyrosine kinase receptor due to BCR-ABL
What symptoms does the patient present with?
- Anemia
- Recurrent infections (low LAP score)
- No neutropenia = no pancytopenia
- Thrombocytopenia
- Heptaosplenomegaly + Lymphadenopathy (Extramedullary hematopoiesis)
- Pruritis following hot showers (basophils secreting histamine, would also been seen in polycythemia vera)
- Gout: high cell turnover (uric acid)
- WBC extremely high = left shift
What are complications associated with CML?
- Recurrent infections= most common cause of death (neutrophila with low LAP score)
- Heart failure (Anemia)
- Renal Failure (high uric acid destroying renal tubules)
- Gout
- CML —AML (blast crisis)
What are treatments for patients with CML?
- Tyrosine Kinase Inhibitor (Imatinib/Gleevec): can also be used to treat GIST in the GIT
- Bone Marrow transplant is definitive treatment
CML can under go a spent phase, what does this mean?
Lots of collagen — secondary myelofibrosis
- -teardrop cells seen in blood
- –dry tap
- only time CML will produce a dry tap and only time we will see tear drop RBCs
Finally the last neoplasm that will be discussed is Primary Myelofibrosis. What is the associated mutation and pathogenesis in this neoplasm?
Mutation in JAK2
—atypical megakaryocytes secrete TGFbeta and PDGF leads to abnormal deposition of collagen — BM fibrosis — pancytopenia
Side note: what other conditions have JAK2 mutations?
- Polycythemia vera
- Essential Thrombocytosis
- SCID
What is the main symptom you see in patients with primary myelofibrosis?
Massive hepatosplenomegaly: due to extramedullary hematopoiesis
What do you see on BM aspirate of patients with primary myelofibrosis?
BM aspirate:
Dry tap due to fibrosis of the BM
What do you see on bone marrow biopsy on patients with primary myelofibrosis?
BM biospy:
Hypocellular marrow
lots of collagen
reticulin stain: stain the collagen black
What do you see on PB smear in patients with primary myelofibrosis?
PB:
Dacrocytes: teardrop shaped RBCs due to fibrosis
Immature WBCs and RBCs (leukoerythroblastosis)
What are complications of Primary Myelofibrosis?
- Recurrent infections - most common cause of death
- Heart Failure
- AML (blasts with greater than 20-25%)
What is the treatment for Primary Myelofibrosis?
Bone marrow transplant
What age do you see CML in?
40-50 year olds
What is leukomoid reaction?
no translocation no basophilia High LAP score (Because neutrophils are normal and not malignant like in CML) Left shift Neutrophilia Elevated WBC count
What population do you see polycythemia vera in?
more common in older ppl 40-60s
Is polycythemia vera a secondary or primary polycythemia?
Primary Polycythemia: because oxygen tension is normal (no hypoxia), EPO levels are very low because of negative feed back you are making to many red blood cells
What is the mutation in polycythemia vera?
JAK2 (also seen in primary myelofibrosis and ET)
Why do patients with polycythemia vera have red cheeks?
Too many red cells so very red complexion
Polycythemia vera can cause hyper viscosity syndrome, what is this?
Symptoms: recurrent symptoms and blurred vision (due to ischemia to retina and cerebral hemispheres)
–syndrome leads to thrombosis (Cells are moving slow because blood is super thick) – infarcts in the spleen and this causes bleeding
On PCR for polycythemia vera, what do you look for?
JAK2 and low EPO levels
Why is iron low in polycythemia vera?
Because your body is using iron to make red cells (serum iron is therefore super low).
–not anemia because you have lots of red cells but a deficiency in iron
What is the treatment for polycythemia vera?
Phlebotomy: bleeding patients out
What is secondary polycythemia?
Low oxygen tension
EPO levels very high because of chronic hypoxia aka COPD and right to left shunts and high altitudes
