Week 2 Flashcards
1
Q
Pancytopenia
A
loss of all cell types, anemia, thrombocytopenia, leukopenia
2
Q
What is a “leuko-erythroblastic picture”?
A
bone marrow cells seen on peripheral blood smear
3
Q
What findings suggest bone marrow pathology?
A
nucleated red cells, basophilic stippling, Howell-Jolly bodies, giant platelets, myelocyte, blasts
4
Q
What 3 things will be obtained in a bone marrow biopsy and why?
A
- Aspirate (.5 cc) for morphologic studies
- Additional aspirate for special studies (5-20cc)
- Core biopsy for histological studies
5
Q
What sample from the bone marrow biopsy will be hemodilute?
A
aspirate for special studies
6
Q
Blasts should make up less than ____% of cell in bone marrow.
A
5
7
Q
Myeloid cells should outnumber erythroid cells by what ratio?
A
2:1 to 5:1
8
Q
How is the cellularity of bone marrow biopsies estimated?
A
100%-age; the rest is fat
9
Q
___ is the best way to gauge a pt’s iron stores.
A
looking directly at bone marrow
10
Q
B cell antigens
A
CD45, CD79a, CD 20, CD 10, kappa and lambda light chain
11
Q
T cell antigens
A
CD45, CD4, 7, 8
12
Q
The most reliable means of counting particular cell types is ____.
A
flow cytommetry
13
Q
The aspirate used in flow cytometry is usually ____. What is done about this?
A
hemodilute; red lysis procedure will lyse erythroid precursors
14
Q
___ scatter in flow cytometry is proportional to cell size.
A
foward
15
Q
___ scatter in flow cytometry is indicative of granules or segmented nuclei.
A
side
16
Q
What are the 2 methods of immunophenotyping?
A
flow cytometry and immunohistochemistry
17
Q
CD34 is a marker of what?
A
hematopoietic stem cells
18
Q
CD33 is a marker of what?
A
granulocytes
19
Q
Routine cytogenetic studies identify and number the chromosomes present in _____ cells.
A
dividing (metaphase)
20
Q
Routine cytogenetics can identify a philedelphia chromosome. This is indicative of what disease?
A
Chromosome 22: Chronic myelogenous leukemia
21
Q
What are the methods of identifying abnormal genotypes?
A
routine cytogenitics, FISH, PCR, complete genome sequencing
22
Q
Describe the philedelphia chromosome and who identified it
A
translocation between 9 and 22. Janet Rowley
23
Q
FISH visualizes cells in what phase?
A
interphase
24
Q
What mutations are needed in AML?
A
Class 1: proliferation advantage
Class 2: impaired differentiation/apoptosis
25
When using PCR to assess an AML pt with normal cytogenetic findings, what 2 samples are used?
leukemia cells, skin biopsy
26
Why is complete genome sequencing unlikely to be a routine clinical procedure?
most mutations are likely irrelevant, epigenetic changes could play a role
27
What type of malignancies arise from mutations in HSC?
1. acute leukemia
2. myeloproliferative disorder
3. Myelodysplastic syndrome (MDS)
28
What HSC malignancy has rapidly proliferative clones, lots of blasts in BM and often blood stream?
acute leukemia
29
What HSC malignancy has chronically proliferating clones which differentiate to circulating cells (normal but high numbers)
myeloproliferative disorder
30
What HSC malignancy has poorly functioning clones (normal number)?
myelodysplastic disorder
31
What is acute myeloid leukemia?
rapidly proliferating clones; blasts in marrow and often blood stream in the myeloid, erythroid, and meg lineages
32
What is acute lymphoid leukemia?
malignancy with rapidly proliferating clones; blasts in bone marrow and often blood stream of lymphocyte lineage
33
What type of acute leukemia appears to be derived from stem cells which have not committed to a lineage?
acute undifferentiated leukemia
34
What are the 3 clinical presentations of acute leukemias?
1. many blasts in blood and marrow
2. few blasts in blood, many in marrow
3. blasts outside marrow such as myeloid sarcoma or lymphoblastic lymphoma
35
A marrow blast number of ____ usually implies acute leukemia.
greater than 20%
36
What are the advantages of genotype diagnostic criteria?
increased prognostic value, predicts response to therapy, identifies moelcular targets for therapy development
37
What 4 things may be used to diagnose?
blast count, blast mophoplogy, imuunophenotype, genotype
38
A mutation in Jak2 is what type of mutation?
Class 1
39
How are the Class 1 and 2 mutations needed for AML identified?
cytogenetic analysis, genomic sequencing
40
Describe the genetics of AML with t(8:21); Runx1-Runx1T1
fusion protein of 2 transcription factor, 5% of AML; dominant negative repressor of myeloid maturation (class 2 mutant). Requires Class 1 mutation concurrently.
41
how is t(8:21) Runx1-runx1t1 identified?
cytogenetics
42
Clinical presentation of pt with AML with t(8:21); Runx1-Runx1T1
younger pt/kids
43
Morphology of AML with t(8:21); Runx1-Runx1T1
some maturation to myelocytes, occasional crystallization of granule contents (Auer rods)
44
Immunophenotype of AML with t(8:21); Runx1-Runx1T1
CD34+, HLA-DR+, CD13+, CD33 weak
45
What is the prognosis of AML with t(8:21); Runx1-Runx1T1
good response to chemo
46
Describe the genetics of AML with t (15:17) PML-RARA
fusion of PML (transcription factor) with RARA (transcription factor) occurs in 5-8% of AML cases. This results in Class 2 dominant negative blockade of differentiation.
47
Clinical presentation of AML with t (15:17) PML-RARA
DIC, severe thrombocytopenia
48
Morphology of AML with t (15:17) PML-RARA
big blasts, cleaved "bat wing" nuclei, many granules, auer rods in stacks
49
immunophenotype of AML with t (15:17) PML-RARA
weak/absent CD34, HLA-DR+, CD13+, CD33+
50
Prognosis and Rx of AML with t (15:17) PML-RARA
Good if diagnosis is made: ATRA is an RA analogue that blocks PML-RARA. It induces differentiation of blasts to granulocytes --> clinical remission
51
HOw is AML with t (15:17) PML-RARA identified?
cytogenetics
52
Auer rods are diagnostic of ____.
AML
53
Describe the genetics of AML with inv(16); CBFB-MYH11
Class 2 dominant negative repressor of myeloid maturaion
54
How is the mutation of AML with inv(16); CBFB-MYH11 identified?
cytogenetics
55
Clinical presentation of AML with inv(16); CBFB-MYH11
younger pt/kids
56
Morphology of AML with inv(16); CBFB-MYH11
mixed granulocyte-monocyte features (myelomonocytic). Increased eosinophilia in blood and marrow
57
Immunophenotype of AML with inv(16); CBFB-MYH11
CD34+, CD117+, CD13+, CD33+, CD14+, CD11b+
58
What markers are found on monocytes?
CD14+ and CD11b+
59
What markers are found on granulocytes?
CD33+, CD13_
60
Prognosis of AML with inv(16); CBFB-MYH11
variably poor; optimal with high dose of cytarabine
61
____% of AML has normal cytogenetics.
40-50
62
Clinical presentation of aml with normal cytogenetics
any age group
63
morphology of aml with normal cytogenetics
undifferentiated, variably granulocytic, monocytic/monoblastic
64
Immunophenotype of aml with normal cytogenetics
Blast markers (CD34,117+), any lineage markers
65
Prognosis of aml with normal cytogenetics
depends on molecular genetics
66
What mutated transcription factors are characteristic of ALL?
IKZF1(KAROS) and PAX5
67
What markers are found on stem cell in the B cell lineage?
CD34;Tdt
68
What markers are found in lymphoid precurors and Pre-B cell
CD19 and 10
69
What markers are found on pre B cell
CD20
70
What mutations are found in ALL?
```
t(9:22) BCR-ABL1
t(?) MLL rearranged
t(12:21) Tel-AML1
Hyperdiploid
Hypodiploid
```
71
Describe the genetics of ALL with t(9;22)BCR-ABL1
fusion protein of BCR to tyrosine kinase (ABL). Proliferative activator, class 1 mutation. IKFZ1 is mutated in most cases. This is a differentiation inhibitor (class 2)
72
Clinical presentation of ALL with t(9;22)BCR-ABL1
25% of ALL in older adults, 2-4% of ALL in kids
73
morphology of ALL with t(9;22) BCR-ABL1
big agranular blasts
74
immunophenotype of ALL with t(9;22) BCR-ABL1
Tdt+. CD10+, CD19+
75
Prognosis of ALL with t(9;22)BCR-ABL1
poor
76
Describe the genetics of ALL with MLL rearrangement
fusion of a transcription regulator to any of several partners. This inhibits differentation so it is a Class 2 mutation. FLT3 is also class 2 and is mutation 20% of time.
77
Clinical presentation of ALL with MLL rearrangement
most common leukemia in kids under one.
78
morophology of ALL with MLL rearrangement
big agranular blasts
79
Immunophenotype of ALL with MLL rearrangement
CD10- CD19+ Tdt+
80
Prognosis of ALL with MLL rearrangement
poor
81
Describe the genetics of ALL with t(12:21) TEL-AML1
fusion protein that acts as a dominant negative transcription factor inhibits differentiation (Class 2). Some show Pax5 deletion.
82
Clinical presentation of ALL with t(12:21) TEL-AML1
25% of pediatric B-ALL
83
Morphology of ALL with t(12:21) TEL-AML1
big agranular blasts
84
immunophenotype of ALL with t(12:21) TEL-AML1
Tdt+, CD34+, CD20-
85
Prognosis of ALL with t(12:21) TEL-AML1
good
86
Describe the genetics of T-ALL
most have a translocation of an oncogene to a TCR promoter. there are 3 possible TCR loci and multiple partners.
87
Clinical presentation of T-ALL
kids. 25% often with thymic mass of lymph node, spleen involvement
88
Morphology of T-ALL
big agranular blasts
89
Immunophenotype T-ALL
Tdt+, CD3+, CD5+
90
Prognosis of T-ALL
high risk
91
___ is a myeloproliferative disease with high WBC where all stages of granulocyte maturation end up in blood.
CML
92
What are all the types of myeloproliferative disease stemming from the myeloid lineage?
CML, CMML, rarer forms: chronic eosinophilic leukemia (CEL)/ PDGFR neoplasm, chronic neutrophilic leukemia, mastocytosis
93
What myeloproliferative disease stems from erythroid lineage?
polycythemia vera
94
What myeloproliferative disorder stems from meg lineage?
essential thrombocytopenia or primary myelofibrosis
95
What about a blood smear supports infections etiology rather than neoplastic?
toxic granulation and a left shift composed of progressively fewer cells representing the more immature precursors
96
What about a peripheral smear supports a myeloproliferative neoplasm?
no evidence of toxic granulation, more myelocytes than metamyelocytes (myeloid bulge)
97
What do you look for in bone marrow biopsy that may indicate CML?
increase cellularity, decrease erythroid precursors compared to granulocytes
98
Describe the process of diagnosing CML
CBC+ manual differentiation--> suspect CML--> PCR--> bone marrow biopsy
99
What happens if CML is left untreated?
can progress to acute leukemia
100
___% of the time, pt with CML will have normal cytogenetics.
10
101
___ plays a big role in the growth and migration of mast cells.
SCF
102
What symptoms are associated with mastocytosis? What test should be ordered?
flushing, abdominal pain, tachycardia, hypotension, serum tryptase
103
Neoplasms of mast cells are usually present as _____
benign cutaneous lesions in kids
104
Bone marrow findings for mastocytosis
bland looking cells, round or spindle shaped. sometimes with eosinophilia
105
Genetics of mastocytosis
either cKIT mutants or PDGFRA activation
106
___% or mastocytosis is assocatiated with a second hematologic malignancy.
30
107
Immunophenotype of mastocytosis
tryptase, CD117 (cKIT is the SCF receptor), CD25
108
Polycythemia vera genetics
Jak2 mutation in 95% of cases
109
Polycythemia vera clinical presentation
thrombosis, hypertension, stroke, MI, increased RBC may also be due to lung disease
110
Polycythemia vera morphology
hypercellular marrow, erythroid hyperplasia, increased Megs
111
Polycythemia vera prognosis
10 year survival common, can progress to myelofibrosis, MDS, acute leukemia
112
____ has increased RBCs with hypertension and thrombosis.
Polycythemia vera
113
Essential thrombocytopenia genetics
Jak2 in 50% of cases
114
Essential thrombocytopenia clinical presentation
thombosis, increased platelets can be due to iron deficiency, infection, chronic inflammation
115
Essential thrombocytopenia morphology
increased megs (large and weird looking)
116
prognosis Essential thrombocytopenia
10 year survival common, can progress to myelofibrosis, MDS, acute leukemia
117
Primary myelofibrosis genetics
Jack 2 in 50% of cases
118
Primary myelofibrosis clinical presentation
thrombosis, thrombocytopenia and/or leukoerythroblastic picture
119
Primary myelofibrosis morphology
increased megs, bizarre shape/clustering
120
Primary myelofibrosis prognosis
usually shorter than ET, can progress to marrow failure acute leukemia
121
Myelodysplasias usually present in ____.
elderly patients
122
What are the 5 adult forms of myelodysplasia from best to worst?
refractory cytopenia with unilineage dysplasia, refractory anemia with ring sideroblasts, myelodysplastic syndrome with isolated del, regractory cytopenia with multilineage dysplasia, refractory anemia with excess blasts
123
refractory cytopenia with unilineage dysplasia clinical presentation
unexplained cytopenia in elderly patients
124
refractory cytopenia with unilineage dysplasia morphology
weird precursors, binucleation or irregular nuclei, can show fibrosis, high or low cellularity, megaloblastoid features
125
refractory cytopenia with unilineage dysplasia prognosis
survival not clearly less than normal for age
126
refractory anemia with ring sideroblasts clinical presentation
unexplained cytopenia in elderly patients
127
refractory anemia with ring sideroblasts morphology
ring sideroblasts with dyspoietic features in red cell series only
128
refractory anemia with ring sideroblasts prognosis and diagnosis
Prog: survival not clearly less than normal. Dia: morphologic findings and iron stain
129
MDS is isolated del(5q) clinical presentation
severe anemia in elderly women
130
MDS is isolated del(5q) morphology
all megs are mononuclear
131
MDS is isolated del(5q) prognosis
good median survival, treatable with lenalidomide, 10% progress to AML
132
Refractory cytopenia with mutlilineage dysplasia clinical presentation
severe anemia in elderly women
133
Refractory cytopenia with mutlilineage dysplasia morphology
granulocytes dont granulate normally, nuclei dont lobulate normally
134
Refractory cytopenia with mutlilineage dysplasia prognosis
median survival is 30 months, 10% progress to AML
135
refractory anemia with excess blasts clinical presentation
cytopenias in elderly patients
136
refractory anemia with excess blasts morphology
blasts and dyspoietic maturation
137
refractory anemia with excess blasts immunophenotype
CD34+ and CD117+ population
138
refractory anemia with excess blasts types and prognosis
RAEB-1: 5-9% blasts, 1/4 go to AML
| RAEB-2: 10-19% blasts, 1/3 to to AML
139
Symptoms of bone marrow failure
anemia, neutropenia, thrombocytopenia
140
___ most common cancer in children
ALL
141
What acute leukemia is a disease of adults and elderly?
AML
142
What is the difference between primary and secondary AML?
primary: de novo, easier to treat
secondary: from MDS, harder to treat
143
Treatment of AML
1. remission induction therapy
2. post remission therapy
3. maintenance therapy/ bone marrow transplane
144
Strategies for treatment of AML in older adults
supportive care, chemo, new noncytotoxic agents (Azacitidine), reduced intensity conditioning
145
What genetic abnormalites of ALL are associated with poor outcome?
MLL, BCR-ABL1
146
What genetic abnormalities of ALL are associated with good outcome
hyperdiploidy, E2A-PBX, TEL-AML
147
Treatment of ALL
3 treatment phases, allopurinol, CNS prophylaxis
