MYELOPROLIFERATIVE NEOPLASMS Flashcards
Caused by genetic mutations in the stem cell that causes excessive production and accumulation of RBCs, granulocytes and platelets in the Bone Marrow, Blood and tissues
MYELOPROLIFERATIVE NEOPLASMS
Philadelphia chromosome t(9;22)
CML
JAK2 gene mutation (90-95% of cases)
PV
JAK2 gene mutation (50% of cases)
ET
JAK2 gene mutation (50% of cases)
PMF
Arises from a single genetic translocation in a pluripotential HSC producing a clonal overproduction of the myeloid cell line
CHRONIC MYELOGENOUS LEUKEMIA
Associated with Philadelphia Chromosome
CHRONIC MYELOGENOUS LEUKEMIA
Translocation between the long arms of Chromosomes 9;22 (_______)
Philadelphia Chromosome
Lab findings:
Increased Total WBC Count (>50x10^9/L)
- increased in mature forms of granulocytes – Neutrophils, Eosinophils, Basophils
- Normal or increased platelet count
- Normal or decreased RBCs
CHRONIC MYELOGENOUS LEUKEMIA
Differential Diagnosis:
Must be differentiated from Leukemoid reactions thru NAP cytochemical staining
CHRONIC MYELOGENOUS LEUKEMIA
NAP score for CML
Lower
Increased or Normal NAP score
Leukomoid reaction
Differential Diagnosis:
________ transplantation has been successful, and ________ ( tyrosine kinase inhibitor) produces remission in most cases of CML
Bone Marrow
imatinib mesylate
The neutrophil Alkaline phosphatase (NAP) is greatly ________ or ________ in >90% of patients with CML
reduced
absent
NAP
Spx:
Blood film
NAP
Dye:
Diazo (alkaline pH)
NAP
Product:
insoluble blue compound
NAP
Evaluated 100 neutrophils
Grading: 0
no staining
NAP
Evaluated 100 neutrophils
Grading: 1+
faint/diffuse
NAP
Evaluated 100 neutrophils
Grading: 2+
pale/moderate
NAP
Evaluated 100 neutrophils
Grading: 3+
strong blue ppt
NAP
Evaluated 100 neutrophils
Grading: 4+
deep blue without visible cytoplasm
Reference Interval for NAP:
15-170
- Characterized by excessive proliferation of erythroid, granulocytic and megakaryocytic elements in the bone marrow (panmyelosis).
- Splenomegaly is usually present
POLYCYTHEMIA VERA
WHO criteria for diagnosis for PV:
- _______ Hemoglobin, Hematocrit, or red cell
mass
- ________ Bone Marrow with trilineage growth (________)
- Identification of the________ mutation or the
________ mutation
- _____ EPO levels
Increased
Hypercellular
panmyelosis
JAK2 V167F
JAK2 exon 12
Low
WHO criteria for diagnosis for PV: (Ref. range)
Men: Hgb > ____ g/dL and Hct > %
Women: Hgb > ____ g/dL and Hct > ____ %
16.5 and 49
16 and 48
Treatment for PV:
- Therapeutic phlebotomy
- Alkylating agent hydroxyurea
- JAK inhibitor (eg. Ruxolitinib)
Clonal MPN with increased megakaryopoiesis and thrombocytosis
ESSENTIAL THROMBOCYTHEMIA
ESSENTIAL THROMBOCYTHEMIA
Clinical Manifestations:
- ________ (thromboses in major arteries and veins)
- _______ resulting to atrophy
- Pulmonary ______ and neurologic complications
- Bleeding in mucous membranes
Vascular Occlusions
Splenic infarcts
emboli
ESSENTIAL THROMBOCYTHEMIA
Lab Findings:
- Thrombocytosis (>400 x 109/L)
- Platelets often appear normal, but there could be presence of _____ bizarre platelets, platelet aggregates, micro megakaryocytes, and megakaryocyte fragments
- _______ is usually present and ranges from 22-40x10^9/L
- Segmented neutrophils may be _______
giant
Leukocytosis
increased
Treatment for ET:
Plateletpheresis
Hydroxyurea therapy
Low-dose aspirin
JAK2 inhibitors
It is the least common but most aggressive form of MPN
PRIMARY MYELOFIBROSIS
Chronic, progressive clonal panmyelosis characterized by megakaryocytic and often granulocytic hyperplasia with varying degrees of reactive fibrosis of the marrow & extramedullary hematopoiesis
PRIMARY MYELOFIBROSIS
Splenomegaly is present in 90% of patients with PMF and 50% have hepatomegaly
PRIMARY MYELOFIBROSIS
PRIMARY MYELOFIBROSIS
Bone Marrow Findings:
- ______ (megakaryocytic and often granulocytic
hyperplasia)
- Varying degrees of ________
- Collagen _________ disrupting the normal architecture of the Bone Marrow
- It is usually impossible to aspirate marrow, and ______ is necessary for examination
Panmelosis
Reactive fibrosis
overproduction
biopsy
PRIMARY MYELOFIBROSIS
CBC Findings:
- ________ anemia
- anisocytosis
- poikilocytosis
- _______ resulting from fibrosis of Bone Marrow
Normocytic
Pancytopenia
Treatment for PM:
transfusions
hydroxyurea
interferon-y
busulfan
androgens
erythropoietin
JAK2 inhibitors
Historically referred to as refractory anemia, smoldering leukemia, oligoblastic leukemia, preleukemia
MYELODYSPLASTIC SYNDROME (MDS)
MDS
The median age of diagnosis is ___ years old
76
MYELODYSPLASTIC SYNDROME (MDS)
Group of acquired clonal hematologic disorder characterized by:
→ Progressive _______
→ (DDD)
Cytopenia
Dyserythropoiesis
Dysmyelopoiesis
Dysmegakaryopoiesis
FAB classification of MDS:
Refractory anemia
Refractory anemia with ______
Refractory anemia with _____
Chronic __________ leukemia
Refractory anemia with excess _____ in transformation (RAEB-t)
Ring Sideroblasts
Excess Blasts
myelomonocytic
blasts
