[LEC] UNIT 5 Myeloproliferative Neoplasm Flashcards
1
Q
Clonal hematopoietic disorders caused by genetic mutations in
A
Hematopoietic stem cells
2
Q
Mutated gene associated with PV, ET, and myelofibrosis
A
JAK2 gene
3
Q
There is an increase in the percentage of
HSCs and a decrease in the adipocytes in
the bone marrow
A
Hypercellularity
4
Q
Too much platelets would lead to
A
Thrombosis
5
Q
Dysfunctional platelets would lead to
A
Bleeding
6
Q
Hematopoiesis outside the BM due to cell dysregulation
A
Extramedullary Hematopoiesis
7
Q
T or F: Chronic leukemia can transform to acute.
A
T
8
Q
4 Major categories of MPN
A
Chronic Myeloid Leukemia
Polycythemia Vera
Essential Thrombocythemia
Primary myelofibrosis
9
Q
MPN arising from a single genetic translocation in a
pluripotential HSC producing a clonal
overproduction of the myeloid cell line resulting in a preponderance of immature cells in the neutrophilic line
A
Chronic Myeloid Leukemia
10
Q
Chromosome 9
A
ABL
11
Q
Chromosome 22
A
BCR
12
Q
CML is consistently associated with the BCR-ABL 1 fusion gene located in the
A
Philadelphia Chromosome
13
Q
CML occurs predominantly in ages
A
46 to 53
14
Q
CML is commonly seen in populations exposed to
A
Ionizing Radiation
15
Q
T or F: CML detection is often incidental
A
T
16
Q
CML clinical features
A
FABS
Frequent infection
Anemia
Bleeding
Splenomegaly
17
Q
T or F: In CML, there are frequent infections due to decreased level of basophils.
A
F
neutrophils
18
Q
3 phases of CML
A
Initial
Accelerated
Blast crisis
19
Q
Length of each CML phase
A
Initial 2 to 5 years
Accelerated 6 to 18 months
Blast crisis 3 to 4 months
20
Q
Highly treatable phase of CML
A
Initial
21
Q
CML phase that shows partial resistance
A
Accelerated
22
Q
CML phase which is generally unresponsive to treatment
A
Blast crisis
23
Q
CML phase that marks the start of symptoms like splenomegaly and increase in basophils
A
Accelerated
24
Q
Blast crisis contains how many % of blasts in the BM and peripheral blood?
A
30
25
T or F: Those that are not based on Philadelphia
chromosome have a worse prognosis and
are not treated by Imatinib
T
26
T or F: Total WBC is decreased in CML
F
increased
27
What parameters are decreased in CML?
Erythropoiesis
LAP
28
CML other lab findings
Hyperuricemia
Uricosuria
29
2 methods for cytogenetic analysis
Karyotyping
FISH
30
Qualitative reverse transcriptase PCR:
BCR-ABL1 Transcript
31
LAP score of CML
<10%
32
Increased or decreased: Serum cobalamin and transcobalamin in CML
Increased
33
CML Related Diseases
CJ CA
Chronic Neutrophilic Leukemia
Juvenile Myelomonocytic Leukemia (<4 yo)
Chronic Monocytic Leukemia
Adult Chronic Myelomonocytic Leukemia
34
First synthetic tyrosine kinase inhibitor
Imatinib mesylate
35
Designed to selectively bind the ATP binding site
and thus inhibit the tyrosine kinase activity of
the BCR-ABL1 fusion protein
Imatinib Mesylate
36
Neoplastic clonal MPN that commonly manifests
with
Panmyelosis
37
In terms of EPO, the PV px is either
very sensitive
not sensitive
38
Polycythemia Vera is generally characterized by mutation of
Janus Kinase 2 (JAK2V617F)
39
PV occurs predominantly in ages
40 to 60
40
T or F: PV occurs predominantly among women
F
Men
41
Thickening of blood due to increase of blood cells
Paresthesia
42
3 major criteria of PV diagnosis
HEJ
Hypercellularity with trilineage growth
Elevated Hgb, Hct, or red cell mass (RCM)
JAK2V617F mutation or JAK2 exon 12 mutation (Valine translocation)
43
PV Minor criterion
Low serum EPO levels
44
Erythrocytes morphology in PV
Normocytic/normochromic
45
Phases of PV
Proliferative phase
Stable phase
Spent phase
46
PV Phase; Independent of normal regulatory mechanisms
that is associated with increased red blood cell
(RBC) mass
Proliferative Phase
47
T or F: In Proliferative phase of PV, if the red cell increases, plasma content
decreases, blood becomes too viscous
which will affect the heart, also result to
hypertension
T
48
PV presents with ______ _______ quadrant pain
Left upper
49
PV is a triad of
BM fibrosis
Anemia
Splenomegaly
50
Treatment of choice during early stages of PV
Therapeutic phlebotomy
51
Treatment for PV
Therapeutic phlebotomy
Myelosuppressive therapy
Targeted molecular therapy
52
Myelosuppressive therapy uses _____ to
reduce the risk of thrombosis and bleeding in
therapeutic phlebotomy
alkylating myelosuppressive agents
53
PV treatment with JAK2 inhibitors
Targeted molecular therapy
54
A clonal MPN with increased megakaryopoiesis and thrombocytosis
Essential thrombocytopenia
55
Usually with a platelet count greater than 600 x 109/L and sometimes with a count greater than 1000 x 109 /L (1 million)
Essential Thrombocytopenia
56
ET cases predominantly occur in individuals in ages
50 to 60
57
Second peak of ET occurs in what population
Women in the childbearing age (30 yo)
58
ET is also known as
Primary thrombocytosis
Idiopathic thrombocytosis
Hemorrhagic thrombocythemia
59
clot formation inside the blood
vessel that goes with the blood flow
Thrombus
60
Clot causing causing vascular occlusion
Embolus
61
Embolus can travel to the brain through the
Circle of Willis
62
Criteria for Diagnosis
Persistent elevation of platelets
Significant increase (hyperplasia) of megakaryocytes
Not meeting criteria of other MPNs
Demonstration of JAK2V617F or related mutation
63
What parameters are decreased in ET?
Hgb
Hct
Platelet function
64
Treatment of ET that quickly reduces platelet count
Plateletpheresis
65
Treatment for ET
Plateletpheresis
Cytoreductive therapy
Hydroxyurea
Anagrelide
66
Preferred in ET patients with concomitant
thrombocytosis and leukocytosis (at the same time)
Hydroxyurea
67
Splenomegaly and ineffective hematopoiesis
associated with areas of marrow hypercellularity
(leukoerythroblastosis), extramedullary
hematopoiesis, fibrosis, and increased
megakaryocytes
Primary Myelofibrosis
68
Least common but most aggressive MPN
Primary myelofibrosis
69
PM is common in patients in ages
50 and above
70
A reactive process causes overproduction of
collagen that eventually disrupts the normal
architecture of the BM and replaces hematopoietic
tissue resulting in pancytopenia
Myelofibrosis
71
3 types of collagen involved in PM
I
III
IV
72
Collagen type detected via staining with trichome
I
73
Collagen type detected via silver impregnation techniques
III
74
Collagen type detected via radiographic bone density
IV
75
T or F: Increased in collagen are not a part of the clonal
proliferative process but are considered secondary
to an increased release of fibroblastic growth
factors
T
76
PDGF
Platelet Derived Growth Factor
77
TGF-a and -b
Transforming Growth Factor -a and -b
78
IL-1a and 1b
Interleukin 1a and 1b
79
% of major hemolytic episodes in PM
15
80
% of hemosiderinuria and decreased blood
haptoglobin levels (intravascular hemolysis)
10
81
PM Major criteria
Megakarocytic proliferation w/ abnormal morphology
Not meeting criteria of other MPN
Evidence of JAK2V617F or other mutation
82
PM Minor criteria
ALIS
Anemia
Leukoerythroblastosis
Increased serum LDH
Splenomegaly
83
PM Diagnosis requires meeting all three major and ___ minor criteria
two
84
PM prognostic significance
Hgb conc (should be more than 10)
platelet count
osteomyelosclerosis
85
Treatment for PM; JAK2 inhibitor
Momelotinib
86
Most common clinical presentation of Chronic Neutrophilic Leukemia
Hepatosplenomegaly
87
CNL incidence
67 yo
Men = Women
88
CNL diagnosis: WHO criteria requires that the WBC count must be
greater than 25 X 10^9/L, with greater than 90% mature neutrophils and fewer than 10% immature neutrophils
89
T or F: CNL presents abundance of blasts in peripheral blood
F
90
Clonal proliferation of eosinophils from eosinophil
precursors that dominate in the BM and peripheral
blood
Chronic Eosinophilic Leukemia not otherwise specified
91
CEL-NOS diagnosis
Eosinophilia with a count of more than 1.5 X 10^9 cells/L and the presence of malignant features
92
Most common PDGFRA mutation:
fusion gene FIP1L1-PDGFRA
93
T or F: fusion gene FIP1L1-PDGFRA responds well to Imatinib
94
occurs in ATP binding site of PDGFRA
Causes Imatinib Resistance
T6741 mutation
95
# of different fusion genes have been
associated with FGFR1
14
96
Most common fusion genes associated with FGFR1
t(8;13), t(8;9), and t (6;8)
97
high incidence of T-lymphoblastic lymphoma
transformation
t(8;13) fusion gene
98
fusion genes associated with features of CMML
t(8;9) and t(6;8) fusion genes
99
fusion gene that resembles a PV phenotype without eosinophilia
t(6;8) mutation
100
Patients present with features of a chronic myeloid
neoplasm with either ____ or _____
50% to 70% of the time
eosinophilia or BM fibrosis
101
Eosinophilia who do not meet the diagnostic criteria
for a reactive process
Idiopathic Hypereosinophilic Syndrome
102
Heterogeneous group of disorders caused by a
clonal neoplastic proliferation of mast cells (MCs),
which accumulate in one or more organ systems
Mastocytosis
103
No longer considered subgroup of MPNs (2016 Classification system)
Mastocytosis
104
In Mastocytosis, there is a mutation in the _____ gene (Codon 816)
KIT
105
WHO 3 Subcategories of Mastocytosis
Cutaneous M
Systemic M
Localized MC tumors
106
capture disorders that clearly express
myeloproliferative features but either fail to meet
the criteria of a specific condition or have features
that overlap two or more specific conditions
Myeloproliferative neoplasms, unclassified
107
3 groups of MPN, unclassified
early stage of PV, ET, OR PMF
features indicative of advanced disease from clonal evolution
clear evidence of MPN but with concomitant condition
