M3: Myeloproliferative Neoplasms Flashcards
(124 cards)
1
Q
Clonal hematopoietic _____ disorders that result in (excessive/decreased) production and overaccumulation of ______, ______, and _______
A
MYELOPROLIFERATIVE NEOPLASMS (MPNs)
stem cell
excessive
erythrocytes
granulocytes
platelets
2
Q
Clonal hematopoietic stem cell disorders that result in excessive production and overaccumulation of erythrocytes, granulocytes, and platelets in some combination in ____, _____, and _____
A
MYELOPROLIFERATIVE NEOPLASMS (MPNs)
bone marrow
peripheral blood
body tissues
3
Q
has something to do with the bone marrow and hematopoietic cells
A
Myelo
4
Q
Myelo - has something to do with the ______ and ______
A
bone marrow
hematopoietic cells
5
Q
could also refer to myeloid cell series
A
Myelo
6
Q
Myelo - could also refer to _________
A
myeloid cell series
7
Q
proliferate or production
A
Proliferative
8
Q
an abnormal mass of tissue that forms when cells grow and divide more than they should or do not die when they should
A
Neoplasm
9
Q
Neoplasm - an abnormal _____ that forms when cells grow and divide more than they should or do not ___ when they should
A
mass of tissue
die
10
Q
FOUR MAJOR CONDITIONS (WHO)
A
Chronic myeloid leukemia (CML)
Polycythemia vera (PV)
Essential thrombocytopenia (ET)
Primary myelofibrosis (PMF)
11
Q
What is CML
A
Chronic myeloid leukemia
12
Q
What is PV
A
Polycythemia vera
13
Q
What is ET
A
Essential thrombocytopenia
14
Q
What is PMF
A
Primary myelofibrosis
15
Q
Consistently associated with the BCR-ABL fusion gene located in the Philadelphia chromosome
A
Chronic Myelogenous Leukemia (CML)
16
Q
Chronic Myelogenous Leukemia (CML)
Consistently associated with the _____ fusion gene located in the ____ chromosome
A
BCR-ABL
Philadelphia
17
Q
reciprocal translocation of DNA between chromosomes 9 and 22
A
Ph chromosome
18
Q
Ph chromosome – reciprocal translocation of DNA between chromosomes ___ and __
A
9
22
19
Q
Large numbers of myeloid precursors in the bone marrow, peripheral blood, and extramedullary tissues
A
Chronic Myelogenous Leukemia (CML)
20
Q
CML
exhibits leukocytosis with increased myeloid series, particularly the later maturation stages, often with increases in eosinophils and basophils
A
Peripheral blood
21
Q
CML
Peripheral blood - exhibits ____ with (inc/dec) myeloid series, particularly the later maturation stages, often with increases in _____ and _____
A
leukocytosis
Increased
eosinophils
basophils
22
Q
CML
score is dramatically decreases
A
Leukocyte alkaline phosphatase (LAP)
23
Q
What does LAP stand for
A
Leukocyte alkaline phosphatase
24
Q
Leukocyte alkaline phosphatase (LAP) score is dramatically (inc/dec)
A
decreases
25
An enzyme found in the membranes of secondary granules of neutrophils
Leukocyte Alkaline Phosphatase Stain (LAP)
26
LAP
An enzyme found in the membranes of ______ granules of ____
secondary
neutrophils
27
LAP
Purpose: stains __present in most ___
ALP
neutrophil
28
To differentiate CML (↓) from leukemoid reaction or polycythemia vera
Leukocyte Alkaline Phosphatase Stain (LAP)
29
LAP
To differentiate CML (inc/dec) from leukemoid reaction or _____
↓
polycythemia vera
30
↑ leukemoid reaction, _____, ____
polycythemia vera
3rd trimester of pregnancy
31
The degree of reactivity is measured by scoring each of 100 neutrophils according to the amount of precipitated dye present
Leukocyte Alkaline Phosphatase Stain (LAP)
32
LAP
The degree of reactivity is measured by scoring each of _______ according to the amount of precipitated ___ present
100 neutrophils
dye
33
Scored from 0 to 4 (strong)
LAP
34
LAP
Scored from ____ (strong)
0 to 4
35
Heparin must be used
LAP
36
LAP
___ must be used
Heparin
37
LAP
_____ – falsely decreased
EDTA
38
_____ exhibits intense hypercellularity with a predominance of myeloid precursors
CML
Bone marrow (BM)
39
Bone marrow (BM) exhibits intense _____with a predominance of ____
hypercellularity
myeloid precursors
40
______ numbers are normal to increased
CML
Megakaryocyte
41
Patients with CML can progress from a (chronic/acute) stable phase (gradual) through an _____ into transformation to (chronic/acute) leukemia (more rapid)
Chronic
accelerated phase
Acute
42
____ is the preferred approach to treatment CML;
BM Transplantation
43
BM Transplantation
Patients can also be administered with _____.
tyrosine kinase inhibitors
44
the predominant cell type is mature;
Chronic
45
the onset is insidious or gradual but with harmful effects
Chronic
46
Increased WBC count
Chronic
47
Chronic
Increased ___
WBC count
48
Production ins lower from months to years
Chronic
49
Chronic
Production ins lower from _____ to ___
months to years
50
type of leukemia that arises from cells of the myeloid series
Myelogenous:
51
Aside from the presence of _____ proteins, CML also contains the excess production of _____ and one of the targets of CML is the _____
BCR-ABL
Tyrosine kinase
tyrosine kinase inhibitor
52
an enzyme that promotes survival and proliferation of AML cells
Tyrosine kinase
53
Tyrosine kinase: an enzyme that promotes survival and proliferation of ____
AML cells
54
What does AML stand for?
Adult acute myeloid leukemia
55
____________: it targets abnormal BCR-ABL protein to block its function causing the CML cells to die
Tyrosine kinase inhibitor
56
Who are the person important for the discovery of PV
William Osler
Dameshek
57
William Osler what year?
1910
58
Dameshek what year?
1951
59
Polycythemia Rubra Vera
William Osler (1910)
60
Clinical description was that of a patient with engorged veins, plethora (swelling in the face and palms), and an elevated red blood cell count
William Osler (1910)
61
William Osler (1910)
Clinical description was that of a patient with ___, ____(swelling in the face and palms), and an elevated ______
engorged veins
plethora
red blood cell count
62
Leukocytosis and thrombocytopenia were recognized as additional features
William Osler (1910)
63
William Osler (1910)
____and _____ were recognized as additional features
Leukocytosis
thrombocytopenia
64
Added PV to the classification of MPNs
Dameshek (1951)
65
Dameshek (1951)
Added PV to the classification of ____
MPNs
66
Main differential diagnosis is that of reactive erythrocytosis due to hypoxia
Dameshek (1951)
67
Dameshek (1951)
Main differential diagnosis is that of ______ due to _______
reactive erythrocytosis
hypoxia
68
Dameshek (1951)
Presence of ______ = erythropoiesis is stimulated
hypoxia
69
Dameshek (1951)
Inc. RBC makes the blood _____ than normal and may lead to ____ and other complication
thicker
blood clots
70
PV is characterized by
Clonal stem cell disorder characterized by hyperproliferation of the ___, ____, and ________
erythroid
myeloid
megakaryocytic lineage
71
requires that three major criteria and one minor criterion be met
WHO diagnostic criteria
72
WHO MAJOR CRITERIA
1. Hemoglobin _____ in men and ____ in women OR Hematocrit ____ in men and _____ in women OR (inc/dec) red blood cell (RBC) mass mean normal
>16.5 g/dL OR >49% - MEN
>>16.0 g/dL OR >48% - WOMEN
inc
73
WHO MAJOR CRITERIA
2. Bone marrow showing hypercellularity for age with trilineage growth (___) including prominent ____, ____, and _____ proliferation with ____, mature megakaryocytes (difference is size)
panmyelosis
erythroid
granulocytic
megakaryocytic
pleomorphic
74
WHO MAJOR CRITERIA
3. Presence of JAK2V617F or ________
JAK2 exon 12 mutation
75
WHO MAJOR CRITERIA
3. Presence of ______ or JAK2 exon 12 mutation
JAK2V617F
76
WHO MAJOR CRITERIA
3. Presence of ___ or _____
JAK2V617F
JAK2 exon 12 mutation
77
there is a change in the normal structure of protein;
JAK2V617F or JAK2 exon 12 mutation
78
there is a switch of amino acid ____ to _____ at position ______ which changes the shape of the JAK2 protein
JAK2V617F or JAK2 exon 12 mutation
Valine (V)
Phenylalanine (F)
617
79
a protein important for controlling the production of blood cells from the hematopoietic stem cells
JAK (Janus kinase)
80
regulator protein for the hematopoietic stem cell production
JAK (Janus kinase)
81
WHO MINOR CRITERION
Subnormal _____ level
serum erythropoietin
82
Additional diagnostic features of PV include
1. Arterial oxygen saturation of _____ (normal) or greater and ___
92%
splenomegaly
83
Additional diagnostic features of PV include
2. Thrombocytosis of greater than _____
400 x 109 platelets/L
84
Additional diagnostic features of PV include
3. Leukocytosis of greater than ______ without fever or infection
12 x 109 cells/L
85
Additional diagnostic features of PV include
4. Increases in ___, ____, or _______ binding capacity
LAP
serum vitamin B12
unbound vitamin B12
86
PV - Clinical Signs and Symptoms
Associated with increased RBC mass – _____
hyperviscosity
87
PV - Clinical Signs and Symptoms
HCT ____ resulting to ____ in about 50% of patients
>60%
hypertension
88
PV - Clinical Signs and Symptoms
Presenting symptoms are associated with _____ and _____ and include headache, weakness, pruritis, weight loss, and fatigue
hyperviscosity
hyperproliferation
89
_____ is a hallmark of PV
Phletora
90
PV - Clinical Signs and Symptoms
_____ has been associated with elevated blood ___ and is often not associated with a ____
Pruritis
histamine
visible rash
91
PV - Clinical Signs and Symptoms
About ____ of PV patients have ____ and ____
experience ______ or ____ episodes
half
thrombocytosis
one third
thrombotic or hemorrhagic episodes
92
Laboratory Data of PV
__ erythrocyte count, packed cell volume, hemoglobin
increase
93
What values are increased in the lab data of PV
erythrocyte count, packed cell volume, hemoglobin
94
Laboratory Data OF PV
Normal ___
erythrocytic indices
95
Laboratory Data OF PV
↓ _____
serum erythropoietin
96
Why is serum erythropoietin is decreased in the lab data of PV
red cell proliferation is thought to be independent of endogenous erythropoietin
97
t/f: red cell proliferation is thought to be dependent of endogenous erythropoietin
false; INDEPENDENT
98
LAB DATA OF PV:
Peak polycythemic values:
→ Hemoglobin of approximately ___
→ Microhematocrit of approximately ___
→ Total leukocyte (white blood cell [WBC]) count
of ___
→ Platelet count of ____
20.6 g/dL
80%
28,000 × 109/L
1,400 × 109/L
99
TREATMENT FOR PV
Therapeutic phlebotomy, myelosuppressive therapy, and targeted molecular therapy
100
a controlled
removal a large volume of blood to reduce volume, red cell mass and iron stores
Therapeutic phlebotomy
101
Characterized by a significant increase in circulating platelets,
Essential Thrombocytosis or Essential
Thrombocythemia (ET)
102
Essential Thrombocytosis or
Essential
Thrombocythemia (ET)
103
Essential Thrombocytosis or Essential
Thrombocythemia (ET) Characterized by a significant increase in circulating ____, usually in ___ of ____
platelets
excess
1,000 × 109/L
104
WHO criteria require a sustained thrombocytosis with a platelet count of _____
400 x 109/L or greater
105
In ET, Elevated ____ may be encountered as a ___, secondary to a variety of ____, or they may represent essential ___,
platelet counts
reactive phenomenon
systemic conditions
thrombocythemia
106
primary disorder of the bone marrow
essential thrombocythemia
107
Essential Thrombocytosis or Essential
Thrombocythemia (ET) is AKA
→ primary thrombocytosis
→ idiopathic thrombocytosis
→ hemorrhagic thrombocythemia
108
WHO diagnostic criteria include the following: (ET)
* MAJOR CRITERIA
1. ___ proliferation with ___ and ___ morphology, little to no _____ or ____ proliferation
2. Rarely, minor (___) ___ in ____
3. Must not meet any criteria for ____-positive ___, ___, ___, ____ or other ____
4. Must demonstrate ____, ___, or ___ mutations
1. Megakaryocyte; large; mature ; granulocyte ; erythroid
2. grade 1; increase; reticulin fibers
3. BCR-ABL1; CML; PV; PMF; MDS; myeloid neoplasms
4. JAK2 V617F; CALR; MPL
109
WHO diagnostic criteria include the following (for ET)
*MINOR CRITERIA
presence of a ___ or absence of evidence of ___
clonal marker
reactive thrombocytosis
110
PB and BM in ET shows:
● Platelets often appear ___, but giant ___ platelets, platelet ___, ____, and ____ fragments can also be observed
normal;
bizarre
aggregates
micromegakaryocytes
megakaryocyte
111
PB and BM in ET shows:
Erythrocytes are ____ and ___, unless ___ is present secondary to excessive ___
normocytic
normochromic
iron deficiency
bleeding
112
PB and BM in ET shows:
Splenic infarction can result in ___, nucleated ____, and ___
Howell-Jolly bodies
erythrocytes
poikilocytosis
113
Treatment for ET:
Treatment is initiated to ___ the ____ and control ___
reduce
platelet count
thrombosis
114
can be used to quickly reduce the platelet count
Plateletpheresis
115
Plateletpheresis uses an ____ machine that only removes ___ and then returns the other components of blood to the ___.
apheresis
platelets
body
116
Results when primary myelofibrosis progeny cells stimulate bone marrow fibroblasts to secrete excessive collagen
Primary Myelofibrosis (PMF)
117
Primary Myelofibrosis (PMF) Results when primary ___ progeny cells stimulate bone marrow ___ to secrete excessive ___
myelofibrosis
fibroblasts
collagen
118
In PMF, Overproduction of collagen eventually
___ the ___ architecture of the ___ and replaces ___ tissue resulting in ___
disrupts;
normal
BM
hematopoietic
pancytopenia
119
decreased production in all types of cells
pancytopenia
120
In primary myelofibrosis, nucleated red blood cells (___) and ___ are released into the circulation (___) when there is ___ hematopoiesis (i.e., ___have taken over blood cell production because of the ___ marrow)
normoblasts
myelocytes
leukoerythroblastosis
extramedullary
non-marrow organs
fibrosed
121
Diagnosis of Primary Myelofibrosis:
MAJOR CRITERIA
● ___ proliferation with ____ morphology, usually accompanied by ___ and/or ___
● Not meeting the criteria for other ___
● Evidence of ___ or other related ___
Megakaryocytic; abnormal; reticulin; collagen fibrosis
MPNs
JAK2V617F; mutations
122
Diagnosis of Primary Myelofibrosis
MINOR CRITERIA
● ____ (presence of nucleated red cells and immature white cells)
● ___
● ____ (Increased/Decreased) ____ levels
●___
Leukoerythroblastosis
Anemia
increased; serum lactic dehydrogenase (LDH)
Splenomegaly
123
presence of nucleated red cells and immature white cells
Leukoerythroblastosis
124
nucleated red blood cells aka
normoblasts
