03.24 - Malignancies from Bone Marrow (Strom) Flashcards
1
Q
14q11 is location of
A
TCR
2
Q
2 components of CBF heterodimer
A
CBFB and Runx1
3
Q
3 AML’s dx by genetics alone (regardless of blast count)
A
t(8;21) RUNX1-RUNX1T1; inv(16) CBFB-MYH11; t(15;17) PML-RARA
4
Q
75% of ALL occur in pts under
A
6
5
Q
80% of acute leukemias in kids are
A
ALL
6
Q
Accelerated phase CML will show what in bone marrow
A
Increased blasts
7
Q
Activating mutation in ET
A
Jak2-v617F or MPL
8
Q
Activating mutation in jak2 mimics presence of
A
EPO
9
Q
Activating mutation in P Vera
A
Jak2-V617F in 95% of cases
10
Q
Auer rods
A
crystallization of granule contents
11
Q
B-ALL’s lack expression of
A
CD3, CD5
12
Q
Bad prognosis ALL subgroups
A
t(9;22) BCR-ABL1; t(v;11q23); MLL rearranged
13
Q
Basic starting point for diff dx
A
PBS manual count
14
Q
BCR-ABL inhibitor
A
Imatinib
15
Q
BCR-ABL1 fusion activates
A
proliferation
16
Q
Bone marrow of CML
A
Hypercellular, many myeloid precursors, little dysplasia, no increase in blasts
17
Q
Both T- and B-ALL’s express
A
TdT
18
Q
CBFB-MYH11 is what genetic lesion
A
inv(16)
19
Q
CD117
A
C-KIT, the SCF receptor
20
Q
CD19+, CD20+ =
A
Mature lymphocytes/lymphoma
21
Q
CD34 =
A
Blasts
22
Q
CD34, CD33 =
A
Myeloid Blasts
23
Q
Cell increased in Primary Myelofibrosis
A
Platelets
24
Q
Clinical presentation MLL rearranged ALL
A
Most common leukemia in kids <1
25
Clinical presentation of BCR-ABL1 ALL
Older adults, kids <1
26
Clinical presentation of CBFB-MYH11 AML
Younger patients/kids
27
Clinical presentation of complex karyotype AML
Any age group
28
Clinical presentation of cyto (-) AML
Any age group
29
Clinical presentation of Essential Thrombocythemia
Thrombosis
30
Clinical presentation of Mastocytosis
Variable and Confusing
31
Clinical presentation of MDS w isolated del(5q)
Anemia, often severe; usually elderly, more women
32
Clinical Presentation of PML-RARA AML
Severe thrombocytopenia
33
Clinical presentation of Polcythemia Vera
Thrombosis, HTN, stroke, MI
34
Clinical Presentation of Primary Myelofibrosis
Thrombosis
35
Clinical presentation of Refractory Anemia w Ring Sideroblasts
Unexplained Cytopenia, usually elderly
36
Clinical presentation of Refractory Anemia with Excess Blasts
Cytopenias; usually elderly
37
Clinical presentation of Refractory Cytopenia w Multilineage Dysplasia
Anemia, often severe; usually elderly, more women
38
Clinical presentation of Refractory Cytopenia w/ Unilineage Dysplasia
Unexplained cytopenia(s), usually elderly patients
39
Clinical presentation of RUNX1-RUNX1T1 AML
Younger patients/kids; Pancytopenia symptoms
40
Clinical presentation of T-ALL
25% of pediatric B-ALL; Often w/ thymic mass or lymph node, spleen involvement
41
Clinical presentation of TEL-AML1 ALL
25% of pediatric B-ALL
42
Common gene in CMML translocations
PDGFRB
43
Common motif for lymphoid malignancies =
oncogene >>> Ig or TCR promoter
44
Consequence of IKZF1 mutation
Inhibits differentiation
45
Cytogenetic (-) w/ FLT3 mutation is subtype of what
AML
46
Cytogenetics in MDS w isolated del(5q)
Only loss of 5q
47
Essential thromb can progress to
Myelofibrosis, MDS, Acute Leukemia
48
First criterion for acute leukemia dx
Blasts >20%?
49
Frequency of Jak2 mutation in Essential Thromb
50% of cases
50
Frequency of Jak2 mutation in Primary myelofibrosis
50% of cases
51
Frequency of Jak2 mutation in Primary Myelofibrosis
50%
52
Genetics of Mastocytosis
Either cKIT mut or PDGFRA activation (FIP1 trans)
53
Good prognosis ALL subgroups
t(12;21) TEL-AML1/ETV6-RUNX1; Hyperdiploid
54
How cyto (-) AML is treated depends on
results of targeted dna sequencing studies
55
Hyperdiploid means
>50 chromosomes
56
Immunophenotye of Essential Thromb
No known features
57
Immunophenotype of BCR-ABL1 ALL
CD10+, CD19+, TdT+
58
Immunophenotype of CBFB-MYH11 AML
complicated
59
Immunophenotype of complex karyotype AML
Blast markers (CD34,CD117)+, typically CD33+
60
Immunophenotype of cyto (-) AML
Blast markers (CD34,CD117)+, typically CD33+
61
Immunophenotype of Mastocytosis
Tryptase, CD117 (C-KIT), CD25 usually
62
Immunophenotype of MLL rearranged MLL
CD10-, CD19+, TdT+
63
Immunophenotype of PML-RARA AML
CD13+, CD33+ (all AML +), Weak/absent CD34 (other AML +), HLA-DR-
64
Immunophenotype of Polcythemia Vera
No known features
65
Immunophenotype of Primary Myelofibrosis
No known features
66
Immunophenotype of Refractory Anemia with excess blasts
Blast population (CD34+, and/or CD117+)
67
Immunophenotype of runx1-runx1t1 AML
CD34+, HL-DR+, CD13+, CD33 weak
68
Immunophenotype of T-ALL
CD3+, CD5+, TdT+
69
Immunophenotype of TEL-AML1 ALL
CD10+, CD20-, CD34+, TdT+
70
In CML, next step after RT-PCR
Bone marrow biopsy
71
Intermediate cytogenetic risk group AML is treated based on
sequencing
72
inv(16)(p13.1;q22) fuses what genes
CBFB-MYH11
73
Lesion in Polcythemia Vera
Activating Jak2 mutations in >95% of cases
74
Megakaryocytes in MDS w isolated del(5q)
All are mononuclear
75
Mitogen that plays significant role in growth and migration of mast cells
SCF
76
More myelocytes than metamyelocytes -
Myeloid Bulge (myeloproliferative)
77
Morphology of BCR-ABL1 ALL
Big agranular blasts
78
Morphology of CBFB-MYH11 AML
Mixed granulocyte-monocyte features; Increased eosinophils in blood and marrow
79
Morphology of complex karyotype AML
Undiff, or variably granulocytic, or monocytic/monoblastic
80
Morphology of cyto (-) AML
Undifferentiated, or variably granulocytic, or monocytic/monoblastic
81
Morphology of Essential Thromb
Increased Megs (large and weird looking, tend to cluster)
82
Morphology of Mastocytosis
Aggregates of bland looking cells, round or spindle shaped, sometimes with eosinophilia
83
Morphology of MDS w isolated del(5q)
All megs are mononuclear
84
Morphology of MLL rearranged ALL
Big agranular blasts
85
Morphology of PML-RARA AML
Big blasts; Cleaved "bat wing" nuclei; Many cytoplasmic granules; Auer rods in stacks
86
Morphology of Polcythemia Vera
Hypercellular marrow, Erythroid Hyperplasia, Increased Megakaryocytes
87
Morphology of Primary Myelofibrosis
Increased megs; Bizarre shapes, Clustering; Fibrosis
88
Morphology of Refractory Anemia with excess blasts
Blasts and dyspoietic maturation
89
Morphology of Refractory Anemia with Ring Sideroblasts
Ring Sideroblasts, usually w dyspoietic features (in red cell series only)
90
Morphology of Refractory Cytopenia w Multilineage Dysplasia
Granulocytes don't granulate normally; Nuclei don't lobulate normally
91
Morphology of Refractory Cytopenia w Unilineage Dysplasia
Weird precursors, Binucleation or irregular nuclei
92
Morphology of Runx1-Runx1t1 AML
Some maturation to myelocytes, Occassional Auer rods
93
Morphology of T-ALL
Big agranular blasts
94
Morphology of TEL-AML1 ALL
Big agranular blasts
95
Most common leukemia in kids <1
MLL rearranged ALL
96
Most common site of systemic involvement in mastocytosis
Bone Marrow
97
Most T-ALL's have translocation of
oncogene to a T-cell receptor promoter
98
Myelodysplastic Syndromes usually present as
Unexplained cytopenia, bicytopenia, or pancytopenia
99
Myeloid Bulge
More myelocytes than metamyelocytes
100
Myeloid bulge leads you to
Myeloproliferative
101
Myeloproliferative: Elevated platelets
Essential thrombocytopenia, Primary Myelofibrosis
102
Myeloproliferative: Elevated red count =
Polycythemia Vera
103
Myeloproliferative: High WBC, All stages of granulocyte maturation in blood =
Chronic Myelogenous Leukemia
104
Myeloproliferative: High WBC, Monocytes, Promonocytes, Weird hybrids b/t monocytes and granulocytes =
Chronic Myelomonocytic Leukemia (CMML)
105
Myeloproliferative: Increased Eosinophils =
Chronic Eosinophilic Leukemia, PDGFR neoplasm
106
Myeloproliferative: Increased mast cells
Mastocytosis (primarilty tissue targeted)
107
Myeloproliferative: Increased mature neutrophils
Chronic Neutrophilic Leukeia
108
Neoplasms of mast cells usually present as
Benign cutaneous lesions in kids (urticaria pigmentosa)
109
Other than Essential Thrombocythemia, elevated platelets can be due to
Iron deficiency, infection, chronic inflammation
110
Other than Polcythemia Vera, increased RBC count can be seen in
Lung Disease
111
Pathogenesis of CBFB-MYH11 AML
Dominant negative repression of myeloid maturation
112
Pathogenesis of MLL rearranged ALL
Fusion of transcription regulator to any several partners --> Inhibits differentiation
113
Pathogenesis of Runx1-runx1t1 AML
Dominant negative repression of myeloid maturation
114
Patient with myeloid bulge is more likely to have
myeloproliferative neoplasm
115
Percent of AML w normal cytogenetics
40-50
116
Percent of mastocytoses associated with second heme malig
30%
117
PML-RARA is a subtype of what
AML
118
PML-RARA is what translocation
t(15;17)
119
Polcythemia and Essential thrombocythemia both present with
Thrombosis
120
Polycythemia Vera can progress to
Myelofibrosis, MDS, Acute Leukemia
121
Poorly functioning clones =
Myelodysplastic Syndrome
122
Primary myelofibrosis can progress to
Marrow failure, acute leukemia
123
Problem w. immunophenotyping Acute Leukemia
Many break the rules, show mixed phenotype
124
Prognosis of BCR-ABL ALL
Bad
125
Prognosis of CBFB-MYH11 AML
Better than most if "risk adapted therapy is used
126
Prognosis of complex karyotype AML
Poor
127
Prognosis of cyto (-) AML
Depends on molecular genetics
128
Prognosis of Hyperdiploid ALL
Good
129
Prognosis of TEL-AML1 ALL
Good
130
Prognsosis of MLL rearranged ALL
Bad
131
Progression of MDS w isolated del(5q)
10% progress to AML
132
Progression of Refarctory Cytopenia w Mutlilineage Dysplasia
10% progress to AML; Median survival 30 months
133
Result of PML-RARA fusion
Dominant negative blockade of normal RARA --> inhibits granulocyte differentiation
134
Runx1 is part of a heterodimeric TF called
Core Binding Factor (CBF)
135
RUNX1-RUNX1T1 is what translocation
t(8;21)
136
SCF
Mitogen that plays significant role in growth and migration of mast cells
137
Serum EPO in lung disease vs P Vera
elevated in lung disease, not in P Vera
138
Significant morphologic diff between ET and P Vera
In ET, megs look "bizarre"
139
Stain helpful for early Primary Myelofibrosis
Reticulin --> More reticulin fibers
140
T-ALL's lack expression of
CD20, CD10
141
t(1;19) is what fusion
E2A-PBX1
142
t(12;21) is a subtype of what
ALL (TEL-AML1)
143
t(12;21) is what fusion
TEL-AML1 (ETV6-RUNX1)
144
t(12;21) is what genes
TEL-AML1
145
t(15;17) is a subtype of what
AML (PML-RARA)
146
t(15;17) is what genes
PML-RARA
147
t(16;16) involves what genes
CBFB-MYH11 (AML)
148
t(5;14) is what fusion
IL3-IgH
149
t(8;21) is a subtype of what
AML (RUNX1-RUNXT1)
150
t(8;21) is what genes
RUNX1-RUNXT1
151
t(9;22) involves what genes
BCR-ABL1
152
t(v;11q23) =
MLL rearrangement
153
T/F: Auer Rods can be seen in reactive conditions
FALSE
154
T/F: The immunophenotype by itself is a good diagnostic system
FALSE
155
Tdt+, CD10 =
Lymphoid Blasts
156
Toxic granulation and left shift support what etiology
Infectious
157
TP53 mutated AML are typically
complex karyotype (unfavorable cytogenetics)
158
Trick for t cell markers
single digits
159
Tx of MDS w isolated del(5q)
Lenalidomide
160
Tx of PML-RARA fusion
ATRA causes differentiation
161
What else has bizarre megs, other than ET
Primary Myelofibrosis
162
What is mutated in 84% of BCR-ABL1 ALL
IKZF1 TF
163
When mastocytosis spreads beyond skin
Release histamine and other mediators --> systemic symptoms (flushing, tachycardia, hypotension)
164
When to suspect myeloproliferative disorders
High WBC but no infection
165
Why is knowing features of PML-RARA AML so important
Prognosis is good if treated
166
Workup of suspected hematologic disease always begins with
review of peripheral smear
