Heme Malignancies I Flashcards
1
Q
t(11:14)
A
Mantle cell lymphoma (Non-Hodgkin’s Lymphoma)
2
Q
Which leukemia highly associated with DIC?
A
APL
3
Q
“Core binding factor” leukemia and it’s associated cytogenetics
A
Acute myelomonocytic leukemia - inv(16:16)
4
Q
Gingival hyperplasia
A
AML
5
Q
Heart-shaped/bat wing nuclei?
A
APL
6
Q
Arsenic MOA?
A
Breaks down PML-RARalpha fusion protein
7
Q
BBW for Arsenic?
A
CV - QT prolongation, AV block, etc
8
Q
CD14+/CD11b+
A
Acute myelomonocytic leukemia
9
Q
Definition of class I hypothesis
A
Fusion gene causes constitutively active pro-proliferation gene
10
Q
Definition of class II hypothesis
A
Fusion gene acts as a corepressor, inhibiting differentiation
11
Q
AML translocations fit under class ___ hypothesis
A
II (inhibits differentiation of myelocytes)
12
Q
AML associated with eosinophilia?
A
Acute myelomonocytic leukemia
13
Q
Epidemiology of hairy cell leukemia?
A
Middle aged (~40yo) male
14
Q
Most common cutaneous lymphoma and its cell?
A
Mycoses fungoides - Sezary cell
15
Q
Which AML does NOT have CD34+ immunophenotype?
A
APL
16
Q
Which method used to asses immunophenotype?
A
Flow cytometry
17
Q
First step in workup of any heme disease
A
PBS
18
Q
Five criteria to classify something as a blast
A
- Big cell 2. Increased cytoplasm:nuclear ratio 3. Immature chromatin 4. Large nucleus (may be >1 nucleus) 5. Bunch of cells that look alike
19
Q
3 steps in bone marrow aspiration
A
- Half cc of bloody aspirate 2. 5-20 cc in same spot for special studies 3. Core biopsy from different site
20
Q
Purpose of core biopsy in new spot
A
Will not contain blood if you draw from same site where aspirate was done
21
Q
Normal range of myeloid:erythroid precurors
A
2:1 - 5:1 (myeloid should always outnumber erythroid precursors)
22
Q
How to estimate cellularity of bone marrow
A
100-age (rest is fat)
23
Q
Hapten
A
Site where an antigen binds (so a CD is a hapten)
24
Q
Flow is a weak method for detecting ____ cells. Why?
A
Erythroid precursors - they’re lysed before flow so they’re underrepresented on scatter plots
25
Side scatter measures \_\_\_\_; front scatter measures \_\_\_\_\_.
Side scatter measures complexity (granules, seg nuclei); front scatter measures size.
26
On flow scatter plot, x-axis is generally \_\_\_, while y-axis is \_\_\_\_.
X-axis = CD45 (on almost all stem cells in different concentrations) Y-axis - SSC
27
Two immunophenotypes associated with AML's
CD33+(marker for granulocytes)/CD34+(marker for HSC) = myeloid blasts! \*\*Remember: APL NOT assc. with CD34
28
Reed-Sternberg/"owl eyes" cells
HL
29
CD15+/CD30+
RS cell = HL
30
t(9:22) causes what fusion protein?
BCR/ABL in CML
31
MOA of ATRA
Drives differentiation of blasts; tx for PML
32
In which stage of cell cycle must cells be for karyotyping? FISH?
Karyotyping = metaphase FISH = interphase
33
Red probe hybridized to chr9; green probe to chr22. What would CML look like on this FISH?
Yellow (t9:22)
34
Acute leukemias vs. myeloproliferative disorders
Acute leukemias = RAPIDLY proliferating BLASTS Myeloproliferative = CHRONICALLY proliferating DIFFERENTIATED blood cells
35
Which lineages can be involved in acute leukemias?
Myeloid, erthyroid, megakaryocyte
36
What is a myeloid sarcoma?
Acute myeloid LEUKEMIA with monocyte-like features that presents as solid tumors in bone or connective tissue (blasts outside marrow)
37
CD10/CD19 found on:
Lymphoid blasts
38
(T/F): Immunophenotype strongly correlated with response to tx.
False
39
(T/F): Genetics strongly correlated with response to tx.
True
40
Runx1-Runx1T1 is class I or II mutation?
II (AML t8:21)
41
FLT3-ITD is class I or II mutation?
!
42
Inv(16) results in what fusion protein?
CBFB-MYH11 \*remember: acute myelomonocytic leukemia is core binding factor leukemia
43
(T/F): Dominant negative t8:21 sufficient to cause AML
False. Must have class I mutation, too.
44
Leukemia associated with thrombocytopenia?
APL (DIC!!!!)
45
AML prognosis: NPM1 + or CEBPA + and FLT3-ITD -
Poor; HSCT doesn't help
46
AML prognosis: FLT3-ITD+
Good; HSCT helps
47
AML prognosis: NPM1 - and CEBPA - and FLT3-ITD -
Good; HSCT helps
48
How could one immunophenotypically tell apart the B cell ALLs?
t(9:22) = has CD10/19 and TdT t(11:19) = MISSING CD10 t(12:21) = CD34+
49
Imatinib could be used for which of the ALLs?
B cell ALL t(9:22); confers tyrosine kinase activity (class I mutation)
50
Most common ALL in very young pts?
t(11:19)
51
Fusion protein of B cell ALL t(11:19)? Prognosis?
MLL (histone methyltransferase = class II) Bad
52
Gilliand hypothesis doesn't support which ALL?
B-ALL t(12:21)
53
Pax5 mutation seen in which ALL?
B-ALL t(12;21)
54
TRAP stain
Hairy cell leukemia (B-ALL)
55
Only leukemia w/o lymphadenopathy
Hairy cell (B-ALL)
56
Fusion gene of hairy cell leukemia
BRAF-V600
57
Rituximab is tx for which leukemia
Hairy cell (CD20+)
58
IFN2-a,b used for:
Hairy cell leukemia (B-ALL)
59
Dry bone marrow
Hairy cell leukemia (B-ALL)
60
Thymic mass + lymphadenopathy + splenomegaly
T-ALL
61
CD3+
T-ALL
62
Genetic abnormality of T-ALL
Translocation of oncogene to Ig or TCR promoter of chromosome 14
63
Morphology of every ALL (except hairy cell)
Big agranular blasts
64
WHO classification of AML
Blasts \> 20%
65
(T/F): CD13/34 only found in myelogenous malignancies.
False - lymphoid malignancies may also express myeloid markers.
66
75% of ALL presents in pts \< ____ yo
6
67
Class II mutation in B-ALL t(9:22)
IKZF1
68
t(9:22) in B-ALL vs. CML
B-ALL = p190 CML = p210 \*Gene cleaved at different sites
69
Prognosis B-ALL t(9:22)
BAD
70
t(9:22) more common in adult or pediatric ALL?
20% adult ALL; 2-4% of pediatric ALL
71
Most common leukemia in kids \<1 yo
B-ALL t(11:19)
72
B-ALL with class I mutation?
t(9:22); others are class II
73
Prognosis B-ALL t(12;21)
Good! ~90% cure rate!
74
Pax5 deletion (B-ALL t9:22) is a class ___ mutation.
II
75
Adolescent male with mediastinal mass:
T-ALL (thymic mass!!)
76
Relapse of ALL often presents in:
CNS and testis
77
Appearance of granules in lymphocytic leukemias:
ABSENT (agranular cells)
78
Most responsive leukemia to tx?
ALL
79
PML = M\_\_\_
3
80
85% of MALTs associated with:
H. pylori
81
Starry sky
Burkitt's t(8:14)
82
Kid with mass on jaw
Burkitt's t(8:14)
83
Ruddy complexion
Polycythemia ruba vera
84
Increased RBC mass with hypovolemia
Polycythemia
85
"4 H's" of polycythemia
1. Hyperviscosity 2. Hypovolemia 3. Histaminemia 4. Hyperuricemia
86
Blasts + myeloperoxidase positive
AML
87
Tryptase+
Mastocytosis (myeloproliferative)
88
Benzene exposure predisposes to:
CML
89
CML usually ends in:
Blast crisis
90
Progression of CML
Chronic phase --\> Accelerated phases --\> Blast phase
91
AML blasts vs CML blast crisis blasts
AML blasts will have auer rods
92
Tx for chronic phase CML
Imatinib
93
Most common overall leukemia
CLL
94
Myelogenous leukemias present in which age bracket?
Middle age
95
Lymphocytic leukemias present in what age brackets?
Young and eldery ALL usually in kids CLL usually in eldery
96
Basophilia
CML
97
What is a leukomoid reaction?
Normal WBC with left shift; high leukocyte alk phos
98
Low leukocyte alk phos (LAP):
CML (non-functional leukocytes)
99
Affected cell type in CML
Pluripotent stem cell (myelogenous or lymphocytic)
100
Which myeloproliferative disorder associated with possible eosinophilia?
Mastocytosis
101
CKiT mutation:
Mastocytosis (myeloproliferative)
102
CD25+:
Mastocytosis
103
Tear drop cells:
Primary myelofibrosis (myeloproliferative); tear drop PLATELETS
104
Jak2 mutation on chr9 short arm is cause of which three disorders?
Myelofibrosis or polycythemia or thrombocythemia
105
Difference in JAK2 mutation of myelofibrosis vs polycythemia
Myelofibrosis = tyrosine kinase activity Polycythemia = increased growth factor effects
106
What causes myelofibrosis?
Abnormal megs secrete cytokines --\> type THREE collagen deposition in BM --\> extramedullary hematopoeisis
107
60 yo with thombosis, bone pain, muscle wasting, splenomegaly
Myelofibrosis (myeloproliferative)
108
Which lineage most affected in polycythemia?
Erythroid
109
How to tell essential polycythemia from secondary polycythemia?
Essential = DECREASED EPO (trying to reduce the # of RBCs being cranked out by BM) Secondary = increased EPO (trying to compensate for, as an example, high altitude)
110
Generalized pruritis after hot shower:
Polycythemia (heat causes histamine release from excess # of mast cells in polycythemic pt)
111
Prognosis of polycythemia
Progresses to MDS, AML, myelofibrosis
112
Tx of polycythemia
Phlebotomy to deplete iron = less RBC production
113
Cause of thrombocythemia
Excess of dysplastic/abnormal platelets from megs
114
Tx thrombocythemia
Hydoxyurea (ribonucleotide reductase inhibitor)
115
EPO and platelet levels in thrombocythemia
EPO = normal Platelet = extremely elevated
116
Bone marrow with large, multilineage cells
CML
117
Disease that is both a leukemia and a myeloproliferative disorder
CML
118
How do you know when CML pt is in blast crisis?
Smear with \>20% blasts. This will occur in all untreated patients eventually.
119
How to tell CML vs leukomoid reaction
Leukomoid will much more elevated LAP (leukocyte alk phos)
120
Tx for CML? Cure?
Tx = imatinib Cure = allogenic HSCT
121
What's the fusion gene in CML? Class I or II?
BCR-ABL conferring tyrosine kinase activity (why imatinib works). Class I (proliferation).
122
Will CML blasts have auer rods?
NO! Feature of AML!
123
AML
124
There is one leukemia associated with eosinophiia and one myeloproliferative disorder. Name them.
Leukemia = Acute myelomonocytic (inv 16)
Myeloproliferative = Mastocytosis
125
Three heme malignancies associated with JAK2 mutations.
Primary myelofibrosis
Essential thrombocythemia
Polycythemia vera
126
Why muscle wasting in primary myelofibrosis?
Cytokine-like symptom
127
What type of collagen is deposited in bone marrow in primary myelofibrosis? What kind of stain is used?
Type 3 collagen
Reticulin stain for fibers
128
Heme malignancy with decreased EPO?
Polycythemia vera
129
Bone marrow with large, clustered megs
Essential thrombocythemia
130
TPO level in essential thrombocythemia
Normal (megs are pumping out more platelets, not TPO response)
131
What is CMML? Cell type? Labs?
Chronic myelomonocytic leukemia; this is a cross between myeloproliferative and myelodysplastic syndrome
Monocytes, myelocytes, weird hybrids between the two
Leukocytosis
132
PDGF-R mutation
Mastocytosis or CMML
133
Does mastocytosis often present in bone marrow, lymph nodes, or tissues?
Tissues (although the bone marrow is also involved in most cases - cool story, Strom)
134
What "cell" is elevated: PV? ET? Myelofibrosis?
PV = RBC
ET = platelet
Myelofibrosis = platelet
135
Two patients with leukocytosis, fatigue, weight loss, night sweats. How can tell which has an infection and which has a myeloproliferative disorder?
Infection = toxic granulations and left shift with progressively fewer immature cells
MPD = More myelocytes than metamyelocytes ("myeloid bulge"); possible cytogenetic findings (i.e. t9:22 = CML)
136
WBC: 40 K/ul
PMNS: 35
Metas: 15
Myelos: 5
**Sepsis or MPD?**
Sepsis
Left shift
137
WBC: 40 K/ul
PMNs: 26
Metas: 10
Myelos: 20
**Sepsis or MPD?**
MPD
Myeloid bulge
138
What's going on during the accelerated phase of CML?
Increased number of blasts
(but not quite as bad as blasts phase, which is like an acute leukemia)
139
Once CML confirmed via RT-PCR analysis of BCR-ABL protein, why must a bone marrow biopsy still be performed?
Must make sure CML is not progressing to accelerated or blast phase
140
Why does a mutation in JAK2 cause problems with RBCs and platelets?
TPO and EPO are upstream of the JAK2 pathways. So, for example, if the MPL thrombopoeitin receptor of megs is mutated, the same phenoytpe is observed as when JAK2 is mutated (ET).
141
Which MPDs are caused by translocations?
CML, Mastocytosis, CMML
142
Which MPDs are caused by point mutations?
ET, PV
143
What is SCF?
A mitogen involved in mast cell growth and migration
144
Most common presentation of mastocytosis
Urticaria pigmentosa (itchy skin lesions) in a kid
145
What is tryptase?
Mediator secreted by normal and hyperactive mast cells
(Tryptase level elevated in mastocytosis)
146
(T/F): Mastocytosis usually spreads to bone marrow, the most common site of systemic involvement.
False - would be true but mastocytosis usually does NOT spread beyond the skin (urticaria pigmentosa)
147
Kid presents with hypotension, skin lesions, flushing, and itchy skin. What test would you order?
Tryptase levels for mastocytosis
| (or flow looking for CD117,CD25)
148
CD117
Mastocytosis - this is the SCL receptor (remember: SCL is involved in mast cell growth and migration)
149
Man presents with ruddiness, hypertension, and stroke. Dx if EPO low? If EPO high?
If EPO low, PV
If EPO high, secondary polycythemia
150
How to tell PV from ET/myelofibrosis?
PV will have elevated RBCs rather than platelets and will have HTN in addition to thrombosis
ET/myelofibrosis have weird looking megs, PV does not
151
How to tell ET from myelofibrosis?
Myelofibrosis will have more reticulin fibers on reticulin stain than ET
152
WTF is agnogenic myeloid metaplasia?
Another (awful) name for primary myelofibrosis
153
MDS: young or old?
Old
154
del(5q)
MDS
155
Binucleated RBCs
Refractory cytopenia with unilineage dysplasia
156
Prognosis: refractory cytopenia with unilineage dysplasia
Normal for age (usually \>65yo)
157
APL (note many granules + lots of auer rods)
158
Acute myelomonocytic leukemia (note large leukemic blasts with very large nucleoli and heavily vacuolated cytoplasm
159
CML (note many different cell types that are abnormally large)
160
CML
161
CML accelerated phase (more blasts)
162
CML blast crisis (many lineages with excess blasts)
163
ET (lots of platelets and jacked up megs)
164
Primary myelofibrosis (tear drops)
165
Primary myelofibrosis (reticulin stain of type 3 collagen)
166
Primary myelofibrosis (tear drops, type III collagen in BM, reticulin fibers)
167
Why do patients with myelofibrosis have hepatosplenomegaly?
Fibrosis of BM necessitates extramedullary hematopoeisis
168
Mononuclear megs
MDS (del 5q)
169
MDS more common in men or women? Tx?
Women
Lenalidomide
170
Lobulated granulocytes
Refractory cytopenia with multilineage dysplasia
171
RAEB1 vs RAEB2
RAEB1 = blasts 5-9%
RAEB2 = blasts 10-19%
(blasts \> 20% would be an acute leukemia)
172
Polycythemia vera (excessive RBCs)
173
Immunophenotype of refractory anemia with excessive blasts (RAEB)
CD34+/CD117+
174
RAEB vs acute leukemia
Acute leukemia due to translocation, while RAEB due to expansion of cell with mutation that takes over as new cell line
175
Where does iron reside in refractory anemia with ring sideroblasts?
Mitochondria, which make a circle around nucleus
176
Prognosis: Refractory cytopenia with multilineage dysplasia
Poor, ~30 months
177
Prognosis: RAEB
Poor ("pre-leukemia")
178
FAB classification:
AMLs vs ALLs
AMLs = M0-M7
ALLs = L1-L3
179
ALL most common between ages __ - __ and falls off around age __ with a secondary rise around age \_\_\_
3-7
10
40
180
As well as having constitutively active pro-proliferative genes and a block in differentiation, leukemic cells also have:
Reduced apoptosis
181
M0
Undifferentiated
182
M1
Without maturation
183
M2
Granulocyte maturation
184
M3
APL
185
M4
Granulocytic and monocytic maturation
186
M5
Monoblastic (M5a) or monocytic (M5b)
187
M6
Erythroleukemia
188
M7
Megakaryocytic
189
L1
Blasts with high nuclear to cytoplasmic ratio; uniform
190
L2
Larger blasts, lower nuclear to cytoplasmic ratio (more cytoplasm)
191
L3
Vacuolated blasts, basophilic cytoplasm
192
HLA-DR+
193
Bleeding gums
AML
194
MPO+
AML
195
AMLs with good prognosis
t(8:21)
t(15:17)
inv16
**71% 5 year survival**
196
AMLs with intermediate risk
Normal cytogenetics
**46% 5 year survival**
197
AMLs with poor prognosis
3+ chromosomal abnormalities
Monosomies
**16% 5 year survival**
198
Tx shown efficacious in older AML patients
Azacitidine
199
ALLs with worst prognosis
BCR-ABL = t(9:22)
MLL-AF4
200
ALLs with good prognosis
Hyperdiploidy
E2A-PBX
TEL-AML
201
ALL cure rate better in adults or children? Why?
Children
Adults can't handle high dose CTX that is part of curative tx for pediatric ALL
