MIDTERM LECTURE 2: ACUTE MYELOID LEUKEMIA Flashcards
(160 cards)
1
Q
most common type of leukemia in adults
A
AML
2
Q
FAB classification is identified based on
A
morphology and cytochemistry
3
Q
WHO classification is identified based on
A
molecular characterization and cytogenetics
4
Q
General clinical presentation of AML
A
1) decrease production of normal BM elements
2) presence of myeloblast
3) WBC count: 5-30x10^9/L
4) bleeding abnormalities
5) infiltration of malignant cells into the gums and other mucosal sites
6) CNS related symptoms
5
Q
wbc count of px w/ AML
A
5-30x10^9/L
6
Q
bleeding abnormalities in AML is associated with what disorder
A
disseminated intravascular coagulation (DIC)
7
Q
clinical findings in AML
A
1) anemia
2) thrombocytopenia
3) neutropenia
4) pallor
5) fatigue
6) fever
7) bruising
8) bleeding
9) splenomegaly
8
Q
anemia in AML is due to
A
overproduction of blast cells
9
Q
neutropenia in AML is due to
A
blast cells tend to forget to mature
10
Q
how many percentage of px w/ can be seen with splenomegaly
A
50%
11
Q
abnormalities in laboratory results in AML
A
1) hyperuricemia
2) hyperphosphatemia
3) hypocalcemia
4) hypokalemia
12
Q
cause of hyperuricemia in AML
A
caused by increased cellular turnover
13
Q
cause of hyperphosphatemia
A
due to cell lysis
14
Q
cause of hypocalcemia
A
hyperuricemia and hyperphosphatemia involves in bone destruction
15
Q
group of metabolic complications that occurs in px with malignancy, with or without treatment
A
tumor lysis syndrome
16
Q
tumor lysis syndrome is notable in what diseases
A
lymphoma and leukemia
17
Q
tumor lysis syndrome is caused by
A
breakdown of the products of dying cancer cells
18
Q
how does tumor lysis syndrome lead to renal failure
A
dying cancer cells products-> acute uric acid nephropathy-> renal failure
19
Q
tumor lysis syndrome is characterized by
A
hyperkalemia
hyperphosphatemia
hyperuricemia
hyperuricosuria
20
Q
subtypes of AML according to WHO classification
A
1) AML w/ recurrent genetic abnormalities
2) AML w/ myelodysplasia-related changes
3) therapy-related myeloid neoplasms (t-MNS)
4) AML, not otherwise specified
5) Myeloid Sarcoma
6) Myeloid Proliferations Related to Down Syndrome
7) Blastic Plasmacytoid Dendritic Cell Neoplasm
8) Acute Leukemias of Ambiguous Lineage
21
Q
AML with recurrent genetic abnormalities
A
1) Acute myeloid leukemia with t(8;21)(q22;q22.1); RUNX1/RUNX1T1
2) AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFV-MYH11
3) Acute promyelocytic leukemia with PML-RARA
4) AML with t(9;11)(p22;q23); KMT21A (MLL)-MILLT3
5) AML with t(6;9)(p23;q34.1); DEK-NUP214
6) AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM (RPN1-EVI1)
7) AML with t(1;22)(p13.3;q13.3) RBM15-MKL1
8) AML with BCR-AML1
9) AML with gene mutations
10) AML with mutated NPM1
11) AML with biallelic mutation of CEBPA
12) AML with mutated RUNX1
22
Q
identify the mutation:
AML with t(8;21)(q22;q22.1)
A
RUNX1-RUNX1T1
23
Q
identify the mutation:
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22)
A
CBFB-MYH11
24
Q
identify the mutation:
AML with t(9;11)(p22;q23)
A
KMT21A (MLL)-MLLT3
25
identify the mutation:
AML with t(6;9)(p23;q34.1)
DEK-NUP214
26
identify the mutation:
AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)
GATA2, MECOM (RPN1-EVI1)
27
identify the mutation:
AML with t(1;22)(p13.3;q13.3)
RBM15-MKL1
28
identify the AML:
-seen predominantly in children and young adults
-prognosis is favorable but may be negatively affected due to addition of abnormalities
RUN X1/RUNX1T1
29
AML RUNX1/RUNX1TI is found in how many percent of AML cases
5%
30
RUNX1/RUNX1T1 is diagnosed based on
genetic abnormality
31
RUNX1/RUNX1T1 clinical findings
-myeloblast w/ dysplastic cytoplasm
-auer rods
32
RUNX1/RUNX1T1 anomalies
-pseudo-Pelger-Huet cells
-hypogranulation
-eosinophilia
33
CBDB-MYH11 is also classified as what AML
Core-binding factors (CBF) AML
34
AML CBFB-MYH11 accounts for how many percentage of AML cases
5-8%
35
age of px that can develop Core-binding factors (CBF) AML
all ages
36
CBFB-MYH11 is predominant in what age
younger patients
37
diagnosis for CBFB-MYH11
genetic aberration
38
CBFB-MYH11 increases the incidence of what disease
extramedullary disease
39
common site for relapse in CBFB-MYH11
central nervous system
40
T or F:
remission is good in CBFB-MYH11
T
(but only 1/2 are cured)
41
identify the AML:
-characterized by differentiation block at the promyelocytic stage
APL w/ PML-RARA
42
percentage of PML-RARA in AML cases
5-10%
43
what age is PML-RARA predominant
young adults
44
diagnosis for PML-RARA
15;17 translocation
45
subtype of APL that accounts for 13-40% of APL cases and gives an appearance of having no granules
microgranular variant
46
how to differentiate APL with AML
1) auer rods
2) butterly/coin-on-coin nucleus
3) clinical presentation
47
treatment for APL w/ PML-RARA
1) All-trans-retinoic acid (ATRA)
2) Arsenic trioxide
48
what treatment of APL w/ PML-RARA is a vitamin A analogue and induces differentiation of malignant promyelocytes
ATRA
49
identify the AML:
-represents AML subgroups w/ 11q23 abnormalities
KMT2A (MLL)-MLLT3
50
what AML translocation is rare
AML with t(9;12)
51
characteristics of KMT2A (MLL)-MLLT3
1) large blast w/ abundant cytoplasm
2) fine nuclear chromatin
3) motile cells w/ pseudopodia
52
T or F:
KMT2A (MLL)-MLLT3 is frequently seen in adults
F
(frequent in children)
53
KMT2A (MLL)-MLLT3 is associated with what conditions
associated with gingival and skin involvement and DIC
54
identify the AML:
-20% blast cells
-multilineage dysplasia
-history of MDS/MPL
-MDS-associated cytogenetic abnormality
AML w/ myelodysplasia-related changes
55
AML w/ myelodysplasia-related changes should have the absence of what AML
AML w/ recurrent genetic abnormalities
56
AML w/ myelodysplasia-related changes primarily affects what age group
older adults
57
morphologic criteria for multilineage dysplasia
50% dysplasia in 2 lineages
58
significant dysplastic morphology of AML w/ myelodysplasia-related changes
1) pancytopenia w/ neutrophil hypo/hypergranulation
2) pseudo-Pelger-Huet cells
3) unsually segmented nuclei
59
describe the erythrocyte precursors of AML w/ myelodysplasia-related changes
1) vacuolated
2) karyorrhexis
3) megaloblastoid features
4) ring sideroblast
60
genetic findings of AML w/ myelodysplasia-related changes
complex karyotypes, -7/del(9q), and 5/del(5q)
61
identify the AML:
-accounts for 10-20% of AMLs, MDSs, and MDSs/MPNs
-occurs secondary to treatment/malignancy
AML w/ therapy-related myeloid neoplasm (T-MNs)
62
Classifications of AML w/ TMNS
1) therapy-related MDS
2) AML (t-AML)
3) myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN)
63
contributors for developing AML w/ T-MNs
1) alkylating agents
2) radiation
3) topoisomerase II
64
prognosis of AML w/ T-MNs
poor
65
what therapy-related neoplasm mutation behave more like the de novo counterparts
t(15;17) and inv(16)
66
identify the AML:
-occurrence of extramedullary proliferation of blast of one or more lineages
-disrupts the tissue architectures
myeloid sarcoma
67
commonly affected tissues in myeloid sarcoma
1) skin
2) GI tract
3) lymph nodes
68
10% of newborns that are present with abnormal myelopoiesis have what genetic abnormality
trisomy 21
69
identify the AML:
-spontaneous remission occurs within few months
-associated with GATA1 mutations
Myeloid proliferations related to down syndrome
70
Myeloid proliferations related to down syndrome has AML during the first 5 years of life increase by how much
fiftyfold
71
leukemia lineage of myeloid proliferations related to down syndrome
megakaryocytic lineage
72
treatment for myeloid proliferations related to down syndrome
chemotherapy
73
prognosis of myeloid proliferations related to down syndrome
young children: responds well
older children: do not fare
74
identify the AML:
-rare clinically aggressive tumor
-present skin lesions
-may progress involving peripheral blood and BM
Blastic Plasmacytoid Dendritic Cell Neoplasm
75
Blastic Plasmacytoid Dendritic Cell Neoplasm is derived from what precursors
plasmacytoid dendritic cell
76
AML category that do not fit into WHO subtypes
AML, not otherwise specified
77
WHO classification of AML not otherwise specified is identified according to
1) morphology
2) cytometric phenotypic
3) limited cytochemical reactions
78
FAB classification of AML not otherwise specified is identified according to
1) cell origin
2) degree of maturity
3) cytochemical reactions
4) limited cytogenetic features
79
AML, not otherwise specified requires how many percentage of blast to be diagnosed
20%
80
AML, not otherwise specified accounts for how many percent of AML cases
15%
81
FAB classification of AML with minimal differentiation
M0
82
blast description of AML with minimal differentiation
CD13+, CD33+, CD34+, CD117+
83
clinical presentation of AML with minimal differentiation
1) auer rods are absent
2) no clear evidence of cellular maturation
84
AML with minimal differentiation accounts how many percent of AML cases
5%
85
T or F:
AML with minimal differentiation is predominant in either infants or adults
T
86
cytochemical stain results of AML with minimal differentiation
1) MPO +
2) SBB +
3) NASDA +
4) ANAE -
5) ANBE -
87
FAB classification of AML without maturation
M1
88
blast description of AML without maturation
CD13+, CD33+
majority of the cases: CD117+, CD34
89
clinical presentation of AML without maturation
1) blasts comprise 90% of nonerythoid cells
2) <10% of leukocytes show maturation to the promyelocyte stage or beyond
3) at least 3% of blasts give positive results with MPO and SBB
90
cytochemical stain results of acute myeloid leukemia without maturation
1) MPO +
2) SBB +
3) NASDA +
4) ANAE -
91
FAB classification of AML with maturation
M2
92
blast description of AML with maturation
1) >20% blast
2) at least 10% maturing cells of neutrophil lineage
3) <20% precursors with monocytic lineage
93
clinical presentation of AML with maturation
auer rods are often present
94
cytochemical stain results of acute myeloid leukemia with maturation
1) MPO +
2) SBB +
3) NASDA +
4) ANAE -
5) ANBE -
95
FAB classification of Acute myelomonocytic leukemia
M4
96
blast description of acute myelomonocytic leukemia
1) has myeloid and monocytoid cells in peripheral blood and BM
2) 20% monocytic cell, neutrophils, precursors
3) monoblast are large w/ abundant cytoplasm
4) cytoplasm w/ small granules and pseudopodia
5) nucleus is large and immature, has contorted nuceloli
97
(+) myeloid antigens in M4
CD13, CD33
98
(+) monocytic antigens in M4
CD14,CD4,CD11b, CD11c, CD64
99
clinical presentation of AML with maturation
elevated WBC count
100
cytochemical staining results of acute myelomonocytic leukemia
1) MPO +
2) SBB +
3) NASDA +
4) ANAE +
5) ANBE +
101
FAB classification of Acute monoblastic and monocytic leukemias
M5a, M5b
102
Acute monoblastic and monocytic leukemias is aka
Schilling's leukemia
103
80% of cells in Acute monoblastic and monocytic leukemia are from what origin
monocytic
104
evidence of maturation in monocytic leukemia
promonocytes that are blast equivalents
105
blast description of Acute monoblastic and monocytic leukemias
1) blast are large w/ abundant, often granular cytoplasm
2) large nuceleoli
3) CD14+, CD4+, CD11b+, CD11c+, CD64
106
clinical presentation of Acute monoblastic and monocytic leukemias
1) extramedullary cutaneous, gingival infection
2) bleeding disorder present
3) nonspecific cytogenetic abnormalities are common
107
Acute monoblastic and monocytic leukemias accounts how many percent of AML cases
5%
108
T or F:
Acute monoblastic and monocytic leukemias is common in younger individuals
T
109
cytochemical staining results of Acute monoblastic and monocytic leukemias
1) MPO +
2) SBB +/-
3) NASDA -
4) ANAE +
5) ANBE +
110
FAB classification of pure erythroid leukemia
M6
111
pure erythroid leukemia is aka
Di Gugliielmo's syndrome
112
blast description of pure erythroid leukemia
1) MDS with excess blast
2) 80% or more eythroid cell in BM
3) >30% are proerythroblast
113
significant dysplastic features of RBC precursors in M6
1) multinucleation
2) megaloblastoid asynchrony
3) vacuolization
114
clinical presentation of pure erythroid leukemia
1) complex arrangement of hypodiploid chromosome number are common
2) ring sideroblast,
3) Howell-Jolly body
115
what chromosomes are frequently affected in pure erythroid leukemia
chromosome 5 & 7
116
prognosis of pure erythroid leukemia
aggressive and rapid
117
cytochemical stain results of pure erythroid leukemia
1) MPO +/-
2) SBB +/-
3) NASDA +/-
4) ANAE -
4) ANBE -
118
FAB classification of acute megakaryocytic leukemia
M7
119
requirement for diagnosis of acute megakaryocytic leukemia
requires 20% blast, 50% megakaryocyte origin
120
clinical presentation of acute megakaryocytic leukemia
1) cytopenia
2) thrombocytosis
3) megakaryoblast size is 3x than small lymphocyte
4) delicate chromatin with prominent nucleoli
5) immature megakaryoblast have light blue cytoplasmic blebs
121
how are megakaryoblasts identified in acute megakaryocytic leukemia
immunostaining
122
what are the antibodies are used in immunostaining for acute megakaryocytic leukemia
specific for cytoplasmic von Willebrand factor or platelet membrane antigens
123
platelet membrane antigens of acute megakaryocytic leukemia
CD41 (glycoprotein IIb)
CD42b (glycoprotein Ib)
CD61 (glycoprotein IIIa)
124
cytochemical stain results of acute megakaryocytic leukemia
1) MPO -
2) SBB -
3) NASDA -
4) ANAE -
5) ANBE -
125
identify the AML:
leukemia with no clear evidence differentiation along singe cell line
acute leukemia of ambiguous lineage (ALAL)
126
ALAL is commonly referred as
acute undifferentiated leukemia (AULs)
127
demonstrate multiplicity of antigens in which it is not possible to determine specific lineage
mixed phenotype acute leukemia (MPAL)
128
techniques used to identify AML subtype
1) flow cytometry
2) cytogenetic analysis
3) molecular testing
129
old yet important technique used to identify AML subtype
cytochemical stain
130
cytochemical stain result of ALL
1) MPO +
2) SBB -
3) NASDA -
4) ANBE -/+ (focal)
5) ANAE -'+ (focal)
130
advantage of cytochemical stains
inexpensive
131
T or F:
lymphocyte exhibit MPO activity
F
132
leukemic myeloblast are usually (positive/negative) for MPO
positive
133
percentage of blast that shows MPO activity
80%
134
auer rods in leukemic blast and promyelocyte test strongly (positive/negative) for MPO
positive
135
maturing granulocyte test strongly (positive/negative) for MPO
positive
136
examples of negative MPO
lymphoblast in ALL
lymphoid cells
137
more sensitive cytochemical stain for early myeloid cells
SBB
138
granulocytes show (positive/negative result) in SBB
positive
139
why does the SBB stain becomes more intense as the granulocyte mature
increase in numbers of primary and secondary granules
140
monocytes show (positive/negative) stain in SBB
negative to weakly positive
141
lymphoid cells show (positive/negative) result in SBB
negative
142
how many enzymes of esterases are present in leukocytes
nine
143
esterases are used to differentiate what cells
myeloblasts and neutrophilic granulocytes from monocytic origin
144
commonly used substrate esters
a-naphtyl acetate and a-naphtyl butyrate
145
T or F:
ANAE and ANBE are specific
F
(both are nonspecific)
146
specific esterase reaction used
Naphthol AS-D chloroacetate
147
why is NASDA specific
only granulocytic cells stain
148
chloroacetate esterase is present in
primary granules of neutrophils
149
auer rods show (positive/negative) stain in SBB
positive
150
what does ANAE reveal
strong esterase activity in monocytes
151
strong esterase activity demonstrated in ANAE can be inhibited with
sodium fluoride
152
granulocyte show (positive/negative) stain in ANAE
negative
153
lymphoid cells show (positive/negative) stain in ANAE
negative
154
monocyte show (positive/negative) stain in ANBE
diffuse positive
155
T or F:
ANBE is more sensitive than ANAE
F
(less sensitive)
156
granulocytes show (positive/negative) stain in ANBE
negative
157
lymphoid cells show (positive/negative) stain in ANBE
negative (although a small positive dot may be seen)
158
T or F:
ANBE is more specific than ANAE
T
159
positive ANBE indicates what type of leukemia
ANBE
