PRELIM LECTURE L3: MYELOPROLIFERATIVE NEOPLASMS Flashcards
Ma'am Mitchao notes-based w/o table (122 cards)
1
Q
clonal hematopoietic disorder caused by genetic mutations in the HSC
A
myeloproliferative neoplasms
2
Q
each myeloproliferative neoplasms is characterized by what cause
A
clonal expansion of one or more myeloid cell line
3
Q
myeloproliferative neoplasms can progress into what condition
A
acute leukemia
4
Q
4 predominant disorders of myeloproliferative neoplasms
A
chronic myeloid leukemia
polycythemia vera
essential thrombocytopenia
primary myelofibrosis
5
Q
chronic myeloid leukemia is caused by what type of mutation
A
single genetic translocation in a pluripotent HSC
6
Q
CML can progress to what disease if left untreated
A
acute leukemia (blast crisis phase)
7
Q
age of CML
A
all, predominant in ages 46-53 years
8
Q
CML represents how many percent of all cases of leukemia
A
20%
9
Q
progression of CML can occur in what two types
A
myeloid type (AML)
lymphoid type (ALL)
10
Q
T or F:
CML is more common in women than men
A
F
more common in men
11
Q
symptoms of CML
A
fatigue
decrease tolerance of exertion
anorexia
abdominal discomfort
weight loss
splenic enlargement
12
Q
present in proliferating HSCs and their progeny in CML; must be identified to confirm diagnosis
A
Philadelphia chromosome (Ph chromosome)
13
Q
in 1960, Ph chromosome was determined as
A
short chromosome 22
14
Q
who described Ph chromosome
A
Nowell and Hungerford
15
Q
Ph is a reciprocal translocation between what chromosomes
A
long arm of chromosome 9 and 22
16
Q
who discovered that Ph is a reciprocal translocation
A
Rowley, 1973
17
Q
what gene mutated in CML
A
BCR-ABL1 gene
18
Q
where does the translocation of BCR-ABL1 gene occurs
A
next to the SH3 domain of AB1 moiety
19
Q
lab finding in CML caused by increased cell turnover
A
hyperuricemia and uricosuria
20
Q
hyperuricemia and uricosuria may be associated with what conditions
A
secondary gout
uric acid stone
uric acid nephropathy
21
Q
15% of px exhibit total WBC count of:
A
> 300 x 10^9/L
22
Q
symptoms of CML are secondary to what causes
A
vascular stasis
intravascular consumption of oxygen by WBCs
23
Q
useful for preliminary differentiation of CML from LR
A
Lap enzyme activity
24
Q
increased cell lap enzyme activity indicates
A
Leukemoid reaction
25
decreased cell lap enzyme activity indicates
CML
26
first forms of therapy for CML
alkylating agents
27
Alkylating agents for CML
nitrogen mustard
busulfan in comibantion with 6-Thioguanine
28
other drugs for CML treatment
Hydroxyurea
6-mercaptopurine
29
treatment that dramatically improves outcomes of px with CML
interferon alpha
30
combined with interferon alpha that increases the frequency of px long term survival
Cytarabrine
31
polycythemia vera is aka
polycythemia rubra vera
32
a neoplastic clonal MPN
polycythemia vera
33
manifestations of polycythemia vera
panmyelosis in BM
increased RBC, granulocytes, platelets in PB
splenomegaly
34
polycythemia vera arises from what cell
HSC
35
incidence of polycythemia vera in Japan
2 cases/million
36
incidence of polycythemia vera in AUS and EU
13 cases/million
37
T or F:
PV is more common in men than women
T
38
T or F:
PV is more common in Jews
T
39
PV occurs often in what age
40-60 years
40
gene mutated in PV
JAK2 gene
41
what enzyme is JAK2 protein
tyrosine kinase
42
clinical presentation of PV
increase RBC mass
high hct (>60%)
hyperviscosity of blood produces
hypertension in 50% of px
headache
weakness
pruritis
weight loss
fatigue
thrombocytosis (half of px)
thrombotic or hemorrhagic episodes (1/3 of px)
43
thrombosis related events in PV
myocardial infarction
retinal vein thrombosis
thrombophlebitis
cerebral ischemia
44
stable phase of PCV can progress to what phase within 10 years of diagnosis
spent phase
45
clinical manifestations in spent phase
splenomegaly/hypersplenism
BM hyperplasia
pancytopenia
46
triad of PV
BM fibrosis
splenomegaly
anemia w/ teardrop shape poikilocyte
47
early stage PV treatment of choice
therapeutic phlebotomy
48
other treatments for PV
low dose of aspirin
alkylating agents
49
alkylating agent for high-risk px
hydroxyurea
50
substitute alkylating agent for younger px with PV
interferon gamma
51
alkylating agent for elderly with PV who develop intolerance or resistance to hydroxyurea
busulfan
52
a clonal MPN with increased megakaryopoiesis and thrombocytosis
essential thrombocythemia
53
essential thrombocythemia is aka
primary thrombocytosis
idiopathic thrombocytosis
hemorrhagic thrombocythemia
54
essential thrombocythemia has usually a count of
>600 x 10^9/L, sometimes >1000 x 10^9/L
55
count of sustained thrombocytosis required by WHO
>/= 400 x 10^9/L
56
incidence rate of essential thrombocythemia
0.6-2.5 cases per 100,000 people per year
57
prevalence rate of essential thrombocythemia
38-57 out of 100,000 people
58
T or F:
essential thrombocythemia is more common with women than men
T
59
major cases of essential thrombocythemia occur in what age
50-60 years
60
second peak of essential thrombocythemia occurs in what age of women
childbearing years (30 years old)
61
three mutations that are considered driver mutation for ET
JAK2 (64.1%)
MPL (4.3%)
CALR (15.5%)
62
px with ET that are negative for all three mutation are referred to as
triple negative
63
clinical presentations of ET
elevated platelet count
vascular occlusion
splenic atrophy
neurologic complications
arterial thrombi
bleeding that often occurs from mucous membranes
64
arterial thrombi in ET can cause
MI
transient ischemic attack
cerebral vascular accident
65
mucous membranes where bleeding often occurs in ET
GI
skin
urinary
URT
66
neurologic complications in ET
headache
paresthesis of the extremities
visual impairments
tinnitus
67
essential thrombocythemia must be differentiated from what conditions
reactive thrombocytosis and other MPN
68
identification of which genes exclude the cases of reactive thrombocytosis
JAK VC17F and MPL W515K/L
69
WHO requires how many major and minor criteria for ET diagnosis
4 major, 1 minor
70
criteria for ET diagnosis
megakaryocyte proliferation w/ large and mature morphology
little to no granulocytes or erythroid proliferation
grade 1 reticulin fibers
must not meet any critera for BCR-ABL1 positive MPN and MDS
must demonstrate JAK2 VC17F, CALR, or MPL mutations
71
minor criterion for ET
presence of clonal markers or absence of reactive thrombocytosis evidence
72
platelets in ET can appear normal but can be accompanied with
giant bizarre platelet
platelet aggregates
micro megakaryocytes
megakaryocyte fragments
73
leukocyte count in ET
22-40 x 10^9/L (leukocytosis)
74
T or F:
neutrophils are normal in ET
F
may be inc
75
other clinical findings in ET
presence of metamyelocytes and myelocytes
mildly elevated basophils and eosinophils
BM hypercellularity
76
treatment for ET
plateletpheresis
alkylating agents
77
alkylating agents for ET
hydroxyurea
anagrelide
78
what can be done for px with intolerance or resistance to hydroxyurea
cytoreduction:
interferon gamma for younger px
busulfan for older px
79
clonal HSC MPN where there is splenomegaly and ineffective hematopoiesis
primary myelofibrosis
80
primary myelofibrosis is previously known as
chronic idiopathic myelofibrosis
agnogenic myelofibrosis
myelofibrosis with myeloid metaplasia
81
areas of marrow hypercellularity (leukoerythroblastosis)
extramedullary hematopoiesis
fibrosis
increased megakaryocytes
82
megakaryocytes are enlarged with
pleomorphic nuclei
coarse segmentation
areas of hypochromia
83
disruption of normal BM architecture in PMF is caused by
over production of collagen
84
myelofibrosis in PMF consists of how many types of collagens
3-5
85
types of collagens in PMF
type I, III, IV
86
percentage of JAK2 V617F in PMF
60% of px
87
percentage of MPL in PMF
5% of px
88
percentage of CLR in PMF
30% of px
89
percentage of TET2 in PMF
7.7-17% of px
90
percentage of ASXL1 in PMF
13-23% of px
91
percentage of EZH2 in PMF
13% of px
92
percentage of CBL in PMF
6% of px
93
percentage of LNK in PMF
3-6% of px
94
percentage of IDH1/2 in PMF
4.2% of px
95
genes in PMF
JAK2 V617F
MPL
CALR
TET2
ASXL1
DNMT3A
EXH2
CBL
LNK
IDH1/2
96
PMF occurs in what age
60 years
97
T or F:
PMF occurs more often in women than men
F
equally often
98
T or F:
PMF manifestation can be asymptomatic or rapid
T
99
symptoms of PMF resulted from anemia, meyloproliferation and splenomegaly
fatigue
weakness
shortness of breath
palpitation
loss of appetite
weight loss
night sweats
pruritis
pain in extremities and bones
bleeding
splenomegaly
100
peripheral blood and bone marrow findings in PMF
quantitative and qualitative abnormalities
leukocytosis with left shift
thrombocytosis
fibrosis
pancytopenia
leukoerythroblastosis
anisocytosis
poikilocytosis
101
treatment for severe anemia in PMF
androgen therapy
prenidisone
danazol
thalidomide
lenalidomide
102
treatment for hemolytic anemia in PMF
glucocorticosteroids
103
MPN that is a clonal disorder with neutrophil hyperproliferation
chronic neutrophilic leukemia
104
chronic neutrophilic leukemia must be differentiated from
CML
myelodysplasia
reactive neutrophilic process
105
incidence of chronic neutrophilic leukemia
rare, only 150 cases reported
106
median age of diagnosis in chronic neutrophilic leukemia
67 years
107
T or F:
male and female are equally affected in chronic neutrophilic leukemia
T
108
most common clinical presentation in chronic neutrophilic leukemia
hepatosplenomegaly
109
clinical presentations of chronic neutrophilic leukemia
fatigue
weight loss
easy bruising
bone pain
night sweats
bleeding from mucocutaneous sites e.g. GI tract (25-30%)
gout
pruritus
110
wbc count in chronic neutrophilic leukemia
25 x 10^9/L
111
neutrophil relative count in chronic neutrophilic leukemia
>80%
112
findings in peripheral blood and bone marrow in chronic neutrophilic leukemia
increase band, metamyelocyte, myelocyte, and promyelocyte
hypercellular BM with predominantly proliferating neutrophils
113
myeloid to erythroid ratio in chronic neutrophilic leukemia
20:1
114
chromosomal abnormalities in chronic neutrophilic leukemia
+8, +9, +21
del (20q)
del (11q)
del (12p)
115
first line of therapy in CNL
hydroxyurea, followed by interferon alpha
116
therapeutic response in CNL lasts for how many months
12 months
117
only curative treatment for CNL
allogenic stem cell transplant
118
prognosis of CNL
slow, smoldering condition
119
px survival with CNL
6 mos to more than 20 years
120
median survival of px with CNL
2 years
121
when CNL progresses to an accelerated phase and unresponsive to treatment, it exhibits
progressive neutrophilia
anima
thrombocytopenia
splenomegaly
122
