Myeloproliferative Neoplasms Flashcards
MPNs are predominantly ________ , not acute
chronic
clonal hematopoietic stem cell diseases with expansion, excessive production and over accumulation of erythrocytes, granulocytes and platelets in some combination; usually aquired
Myeloproliferative neoplasms
disease with overproduction of granulocytes; the cells do differentiate; clonal disorder of HSC (hematopoietic stem cell line)
CML
disease with overproduction of erythrocytes
PV
Disease with increased megakaryopoiesis and thrombocytosis
ET
combination of overproduction of hematopoietic cells and ineffective hematopoiesis with resultant PB cytopenias; fibrosis in BM
PMF
characterized by acquired structural chromosomal abnormality: Philadelphia chromosome t(9;22)(q34;q11.2), creates the fusion gene BCR-ABL1
CML Chronic Myelogenous Leukemia
Which one is the derivative chromosome in t(9;22) in CML?
22
Unique chimeric gene in CML that codes from a protein with enhanced tyrosine kinase activity which leads to increased proliferation and a loss of apoptotic functions
BCR/ABL1
Laboratory findings in CML PB
MK’d leukocytosis, bimodal granulocyte pattern (hallmark), basophilia (Eos can be higher too), Rare nRBC, +/- micromegakaryocytes, increased LD & Uric acid, decreased LAP (stain)
this enzyme is found within secondary granules of neutrophils
Leukocyte ALKALINE phosphatase (LAP)
how do you score the LAP stain? KNOW HOW TO CALCULATE
score 100 cells from 0-4+ and total the scores; 4+ being a cell that has a lot of secondary granules
What is a normal LAP score?
Normal 20-100
Is the LAP increased or decreased in untreated CML?
decreased
Is the LAP increased or decreased in a leukemoid reaction?
normal to increased
Is the LAP increased or decreased in Pregnancy and Polycythemia Vera (PV)?
Increased
What do lab findings look like in CML Bone Marrow?
Marked hypercellularity, decreased normoblasts (decreased RBC production), normal to increased megakaryocytes, pseudo-gaucher cells often, and increased reticulin fibrosis
Most patients are diagnosed in the ______ phase of CML, where blasts are <_____%
chronic; 10%
The ______ phase of CML has a poorer response to therapy, increased anemia, increased clinical symptoms, micromegakaryocytes, etc
Accelerated
Blast crisis is classified as >____% Blasts; worst prognosis
20%
In CML blast crisis extramedually tissues such as the liver and spleen are involved; since the stem cell is affected, blasts can go either way ______ or ______
myeloid or lymphoid
Patients who are Philadelphia Chrom _______ have a worse prognosis than Ph _______ because it progresses more rapidly
NEG; POS
How is CML treated?
Synthetic tyrosine kinase inhibitors such as Imatinib (Gleevec), BM transplant, chemo to reduce WBC
This drug competes for the binding site of the BCR-ABL gene and reduces activity of the tyrosine kinase
Imatinib
Chronic Neutrophilic Leukemia is not CML but its close. What is a big difference between the two?
CNL has an increased LAP (not decreased like CML)
What is Polycythemia Vera’s mutation?
JAK2 V617F
PV has in increase in what?
RBCs/neutrophils/platelets
Main clinical presentation of PV
Pruritus (but also CNS probs, vision, heart occlusions, ruddy complexion, ulcers, weight loss, splenomegaly)
PV bone marrow manifestations
hypocellular, but M:E is normal
BM iron store are decreased
Megakaryocytes are increased
What is the serum EPO level in PV?
below the reference range
Three stages of PV
Prodromal: mild erythrocytosis
Overt: significant increased red cell mass
Spent: pancytopenia, progresive splenmegaly, BM fibrosis and progression to acute leukemia in 15% of patients
Therapy for PV?
Phlebotomy
ET female to male ratio?
2:1
5 criteria for diagnosing ET?
- platelet count >450
- prolif of megakaryocytic line
- meet criteria for MPN,MDS or Myeloid neoplasm
- Positive for JAK2
- Presence of BM iron (help dif from PV)
Clinical presentation of ET
- erythromyalgia
- seizures
- MI
- dizziness
- Platelet dysfunction
ET treatment
combination of hydroxyurea and low dose aspirin
characterized by proliferation of megakaryocytic and granulocytes. At a later stages there is excessive bone marrow fibrosis
Primary Myelofibrosis (PMF)
Three progressive stages of PMF
Prefibrotic Stage: no significant increase in BM fibrosis
Early Stage:
Fibrotic Stage: significant increase in fibrosis
PML lab presentation
Leukoerythroblastosis
- tear drops
- NRBC
- Polychromasia
- Some macrocytosis
- Micromegakaryocytes
PML Bone Marrow
Dry tap due to fibrosis
PML sometimes transforms into what?
acute leukemia especially acute myelomonocytic leukemia
