Myelodysplastic Syndrome & Myeloproliferative Neoplasms Flashcards
What does the BCR-ABL1 fusion protein do?
constitutive activation of several growth pathways
Who gets secondary erythrocytosis?
smokers; people with chronic hypoxia, certain hemoglobin disorders
What is plethora?
dusky, reddish skin
How is MDS diagnosed?
at least 1 persistent cytopenia; evaluate bone marrow and chromosomes
What is CML?
a hematopoietic stem cell disorder assoc. with BCR-ABL1 gene fusion; usually neutrophilic leukocytosis
How is CML diagnosed?
presence of BCR-ABL1 via cytogenetics, FISH, or RT-PCR of mRNA
Which disease is indolent?
ET
Why does hepatomegaly occur in MPN?
extramedullary hematopoeisis
Most cases of PV contain the ____ mutation.
V617F point
PMF eventually progresses to the ____ stage, in which the bone marrow has reticulin fibrosis, the peripheral blood has leukoerythroblastosis, and other organs enlarge because of extramedullary hematopoiesis.
fibrotic
How is ET diagnosed?
incidentally bc of increased platelet counts
What is the incidence rate of CML? Avg. age at diagnosis?
1-2/100,000; 40-50yo
What is the outcome of CML?
80-85% survival
What is ET?
an MPN characterized by sustained thrombocytosis and no granulocytic hyperplasia in the marrow
What does PMF stand for?
primary myelofibrosis
What are paresthesias?
pins-and-needles sensation
In the prefibrotic stage of PMF, the marrow is hypercellular, showing a _____ and _____ proliferation.
granulocytic; megakaryocytic
What is the prognosis of PMF? Survival?
poor if diagnosed in fibrotic stage- median survival 5 years
What is the prognosis of ET?
good; survival 10-15 years or more; an indolent disease
What is RC-UD?
cytopenia of the one of the various lineages (ie anemia, neutropenia)
In the ____ stage of PV, peripheral blood cell counts are increased.
polycythemic
What does MDS stand for?
myelodysplastic syndrome
What are the 2 broad clinical scenarios of MDS?
- 1a/idiopathic 2. 2a/therapy related (t-MDS)
What does PV stand for?
polycythemia vera
What karyotypes can be seen in MDS?
monosomy or deletion of 5 or 7; trisomy 8
What are MPNs?
proliferations of 1+ myeloid lineages
The JAK2 mutation can be found in ____ of cases of PMF.
50%
What is the treatment for CML?
PTKIs: imatinib (Gleevac) and dasatinib
What would be found in a marrow biopsy of CML in the chronic phase?
hypercellularity; granulocytic hyperplasia; small megakaryocytes with round, non-lobated nuclei; no dysplasia
Once MDS has been diagnosed, it is classified as either ____ or ____.
low grade; high grade
PMF eventually progresses to the fibrotic stage, in which the bone marrow has ____, the peripheral blood has _____, and other organs enlarge because of ____.
reticulin fibrosis; leukoerythroblastosis; extramedullary hematopoiesis
PV should always be considered in a pt with a thrombosis of the ____, ____, or _____ vein.
mesenteric, portal, splenic
What are the s/s of PV?
thrombosis of the mesenteric, portal, or splenic vein; headaches; dizziness; visual probs; paresthesias; plethora; itching; splenomegaly; hepatomegaly
Before diagnosing MDS, you should rule out non-neoplastic causes of 2a myelodysplasia: ____, ______, _____, and _____.
certain drugs (chemo); B12, folic acid, and other deficiencies; viral infection; heavy metal (arsenic) and other toxin exposures
What is PV?
an MPN characterized by increased RBC mass (erythrocytosis) accompanied by increased neutrophils and platelets (trilineage hyperplasia)
What are ring sideroblasts?
RBCs that have iron accumulated in the mitochondria that encircle the nucleus- stains blue
What does dysgranulopoiesis look like?
nuclear hypolobation; neutrophils with bilobed nuclei called pseudo-Pelger-Huet cells; hypogranularity
What are the 2 types of high grade MDS?
- refractory anemia with excess blasts-1 (RAEB-1) 2. refractory anemia with excess blasts-2 (RAEB-2)
What is the initial phase of CML, and what are its characteristics?
the chronic phase; normal blasts, increased neutrophils, basophils, and (usu) platelets
What is PMF?
proliferation of the granulocytic and megakaryocytic lineages with eventual progression to myelofibrosis
MPNs are usually associated with abnormalities of genes (translocations, point mutations) that encode _____.
cytoplasmic or receptor protein tyrosine kinase (PTKs)
Untreated MPNs lead to _____, _____, and _____.
- AML or ALL 2. myelodysplasia with ineffective hematopoiesis (MDS) 3. marrow fibrosis and failure
What is common to all MPNs?
increase in 1+ cell types; hypercellular marrow; spleno- or hepatomegaly; insidious onset usually detected by CBC
What is the prognosis for refractory anemia with excess blasts-1 (RAEB-1)? Median survival? Transformation?
poor; median survival 16 mos; 25% of patients transform to AML
Dysplastic changes in at least ____ % of cells in one or more lineages is diagnostic for MDS.
10
What is the bone marrow like in ET?
atypical megakaryocytes are even larger and more bizarre than PMF
____ mutations can be found in 50% of pts with ET.
JAK2
What is the incidence rate of MPNs?
6-10/100,000
What is seen on the PV bone marrow biopsy?
trilineage hyperplasia; clusters of large, bizarre megakaryocytes
What constitutes the BCR-ABL1 gene fusion?
translocation (9;22)(q34;q11.2) on the derivative chromosome 22 (Philadelphia chromosome)
What is the most serious complication of PV?
venous or arterial thrombi
What does dysmegakaryopoiesis look like?
megakaryocytes have hypolobated or non-lobated nuclei; hyperchromatic nuclei; small size
How are PV and PMF different?
no erythrocytosis in PMF
Where does extramedullary hematopoiesis occur?
spleen, liver, lymph nodes
____ eventually progresses to the fibrotic stage, in which the bone marrow has reticulin fibrosis, the peripheral blood has leukoerythroblastosis, and other organs enlarge because of extramedullary hematopoiesis.
PMF
Who gets 1a/idiopathic MDS, and what is the incidence rate?
people over 50; avg age at diagnosis is 70; 3-5/100,000
In the prefibrotic stage of PMF, the marrow is _____, showing a granulocytic and megakaryocytic proliferation.
hypercellular
What is the 2nd phase of CML? What are its characteristics?
the blast phase; essentially acute leukemia (>20% blasts in the blood)
Who gets 2a/t-MDS?
persons exposed to alkylating agents or IR 2-8 years later
Which cells make up the blast phase in CML?
myeloblasts (70%) and lymphoblasts (30%)
What does RC-UD stand for?
refractory cytopenia with unilineage dysplasia
Who gets MPNs?
adults 50-70yo
What is the later stage of PV called, and what characterizes it?
spent phase; prominent fibrosis of the marrow and falling peripheral blood cell counts
What does high grade MDS mean?
myeloblasts account for >5% of marrow cells and/or more than 2% of peripheral blood cells
What is the prognosis of RC-MD? Survival rate? Transformation?
poor- median survival 2.5 years- 10% transformation to AML
What is RC-MD?
low grade MDS with dysplasia in 2 or more lineages
In the ____ stage of PMF, the marrow is hypercellular, showing a granulocytic and megakaryocytic proliferation.
prefibrotic
What is the prognosis for refractory anemia with excess blasts-2 (RAEB-2)? Median survival? Transformation?
poor; 9 mos; 33% of patients transform to AML
What are the treatments of PV?
serial phlebotomy; aspirin; mild chemo
What is MDS with isolated deletion 5q?
low grade MDS assoc. with anemia, increased platelets, and megakaryocytes with small, round, non-lobated nuclei
What is refractory anemia with excess blasts-1 (RAEB-1)?
5-9% blasts in the marrow or 2-4% blasts in the peripheral blood
Nearly all cases of PV have a mutation of the _____ gene that encodes a _____.
JAK2; JAK2 cell signaling protein
What is the intermediate phase of CML?
the accelerated phase
What are the 4 main types of MPNs?
- chronic myelogenous leukemia (CML) 2. polycythemia vera (PV) 3. primary myelofibrois (PMF) 4. essential thrombocytopenia (ET)
What are the 3 types of low grade MDS?
- refractory cytopenia with unilineage dysplasia (RC-UD) 2. refactory cytopenia with multilineage dysplasia (RC-MD) 3. MDS with isolated deletion 5q
What does ET stand for?
essential thrombocytopenia
What does RC-MD stand for?
refactory cytopenia with multilineage dysplasia
What does MPN stand for?
myeloproliferative neoplasms
What does dyserythropoeisis look like?
RBC precursors with nuclear budding, irregular shaped nuclei, lack of coordinated nuclear/cytoplasmic maturity, increased ring sideroblasts
What is refractory anemia with excess blasts-2 (RAEB-2)?
10-19% blasts in the marrow or 5-19% blasts in the peripheral blood
What are dacrocytes?
tear drop RBCs
What are the s/s of CML?
fatigue, weight loss, night sweats, splenomegaly, anemia
What is the prognosis of RC-UD?
relatively good
What are the s/s of ET?
TIAs; digital ischemia with parasthesias; thrombosis of major BVs
What does low grade MDS mean?
myeloblasts account for
What is the treatment for MDS?
stem cell transplant, supportive care, transfusions
What is the prognosis of PV? Survival?
very good- 10-20 years
What is MDS?
hematopoietic stem cell disorder characterized by ineffective hematopoiesis and increased risk of transformation to acute myeloid leukemia (AML)
____ should always be considered in a pt with a thrombosis of the mesenteric, portal, or splenic vein.
PV
MPNs are usually associated with _____ that encode cytoplasmic or receptor protein tyrosine kinase (PTKs).
abnormalities of genes (translocations, point mutations)
What is the prognosis of CML?
poor- median survival 2-3 years
The ____ mutation can be found in 50% of cases of PMF.
JAK2
What does CML stand for?
chronic myelogenous leukemia
