Unit 2: Myeloid Leukemias Flashcards
Most common type of adult leukemia (incidence increases with age)
Acute Myeloid Leukemia
True or false:
All myeloid leukemias are rapidly fatal if left untreated.
true
Acute myeloid leukemia involves a defect of __________.
HSC (CD34+)
In some AMLs you can find Auer rods = condensed to primary granules. This means cells are…
SBB and MPO+ in
myeloblasts or promyelocytes
SBB/MPO + (in mature myelocytes)
What are the two Non-specific Esterase stains (NSEs) – for monocytes?
- α-Naphthyl Butyrate Esterase (NBE)
- α-Naphthyl Acetate Esterase (NAE)
Specific Esterase Stains – stains for myeloid
cytoplasmic granules…used to separate monocyte
precursors from granulocyte precursors
Napthol AS-D Chloroacetate Esterase (NASD)
Diagnosis of acute myeloid leukemia begins with
Peripheral blood and bone marrow examination
WBC count could be variable in AML but most range from…
1 x 109/L - 200 x109/L
AML:
myeloblasts present in ___% of patients
90
Clinical presentation with AML?
- Anemia
- Neutropenia
- Thrombocytopenia
- Possible splenomegaly
- Bone marrow is hypercellular with >20% blasts
What AML clinical presentations lead to pallor, fatigue, bruising, bleeding, and fever?
- Neutropenia
- Thrombocytopenia
- Possible splenomegaly
AML Lab Findings:
_____________ due to increased cell turnover
Hyperuricemia
AML Lab Findings:
_____________ due to cell lysis
Hyperphosphatemia
AML Lab Findings:
__________________ due to progressive bone destruction.
Hypokalcemia
Hyperuricemia, Hyperphosphatemia, and Hypocalcemia are signs of what syndrome?
Tumor Lysis Syndrome – a group of metabolic
complications that can occur in patients with a malignancy
Generalizations for AMLs:
- Many of these are due to mutations activating inappropriate __________ factors
- All of these exhibit variable degrees of dysmyelo-poiesis
(along with all of their other morphological abnormalities!)
transcription
abnormal hyperproliferation of bizarre
granulocyte &/or monocyte precursors
Dysmyelopoiesis
FAB Classification for AMLs:
Acute Myeloblastic (with Minimal Differen-
tiation) (of nucleus)
Mo
FAB Classification for AMLs:
Acute Myeloblastic w/o Maturation (of cytoplasm)
M1
FAB Classification for AMLs:
Acute Myeloblastic with Maturation (of cytoplasm)
M2
FAB Classification for AMLs:
Acute Promyelocytic
M3
FAB Classification for AMLs:
Acute Myelomonocytic
M4
FAB Classification for AMLs:
Acute Myelomonocytic w/Eosinophilic variant
M4(Eo)
FAB Classification for AMLs:
Acute Monocytic
M5
FAB Classification for AMLs:
Poorly differentiated =
M5a
> 20% blast count not
required if __________
found in AML
genetic mutations
Makes up 5% of AMLs; found in children and adults
younger than 60 yo
AML with t(8;21)(q22;q22)
t(8;21) = ______ prognosis
good
[ “It’s 2 good 2 have t(8;21).” ]
AML with t(8;21)(q22;q22):
WBCs have what functional problems?
with phago-cytosis &
chemotaxis
AML with t(8;21)(q22;q22):
Lab findings?
Blasts are large with abundant, dysplastic cytoplasm and numerous primary granules and Auer rods. Sometimes exhibit pseudo-Pelger-Huet.
AML with t(8;21)(q22;q22):
- MPO & SBB _____
- PAS ______
1+
negative
AML with t(8;21)(q22;q22):
SE ___
____ Auer rods
+
+/-
- Rare: 5-8% of all AMLs and occurs at any age (usually young)
- Myeloblasts, monoblasts, and promyelocytes observed
- Also eosinophila with dyplastic changes
AML with inv(16)(p13.1p22)
AML with inv(16)(p13.1p22):
Remission rate is good but only _____ are cured
half
- Makes up 8% of AMLs
- Characterized by a differentiation block in the promyelocyte stage
AML with t(15;17)(q22;q12) – Acute Promyelocytic Leukemia (APL)
Abnormal hypergranular promyelocytes with Auer rods
* Granules can obscure nucleus with abundant cytoplasm & variable
nuclear size & shape.
AML with t(15;17)(q22;q12) – Acute Promyelocytic Leukemia (APL)
AML with t(15;17)(q22;q12) – Acute Promyelocytic Leukemia (APL):
Leukemic cells also have defective retinoic acid receptor (RARα gene), so can be treated with…
TRA (All Trans Retinoic
Acid, a vit. A derivative)
How ATRA treatment work?
pushes pros into finishing maturation, thus causing
remission! (Then attacked with chemo. – a very successful combination.)
Acute Promyelocytic Leukemia (APL) is strongly associated with _______.
DIC
-A promyelocyte’s primary granules are rich in
thromboplastin - like substances . . .which trigger a “bleeding diathesis”.
What is the variant subtype of APL?
microgranular APL (cells look agranular if only light
microscopy used)
Lab Findings FOR BOTH APL VARIANTS:
MPO & SBB =
PAS ____
2+
negative
Lab Findings FOR BOTH APL VARIANTS:
SE ____
Both NSE _____
positive
negative
Lab Findings FOR BOTH APL VARIANTS:
- Frequent Auer rods, can be in bundles (so-called “faggot
cells”). - ↓ plt. count because…
Plts. used up making clots
Acute Myelomonocytic Leukemia (aka. AMML) lab findings:
peripheral blood absolute monocytosis (>___%); many
circulating blasts, pros, immature granulocytes & monos!
* >20% monos AND >20% granulocytes
20
Acute Myelomonocytic Leukemia (aka. AMML) lab findings:
-MPO and SBB still _____
-Both BSEs now start to be ______
positive
positive
Acute Myelomonocytic Leukemia (aka. AMML) lab findings:
- SE still _____
- PAS still ______
-_____ Auer rods
positive
negative
+/-
Acute Myelomonocytic Leukemia (aka. AMML) lab findings:
CD…
CD 11b, CD 4, CD 36, and CD 64
AMML clinical symptoms are the common ones, PLUS…
- CNS & soft tissue involvement
- Ex., gum hypertrophy & skin lesions
Acute Monocytic Leukemia (aka. AMoL)
-Makes up _____% of AMLs
-When _____% leukemic cells are monocytic
5-8
> 80
Acute Monocytic Leukemia (aka. AMoL):
Usually CD ___ and CD ___ pos. (“gold std.”)
4
64
Acute Monocytic Leukemia (aka. AMoL) is usually t(____)
t(8;16)
clinical symptoms of AMoL?
Similar to AMML (with CNS & soft tissue involvements.)
Why is there Increased serum & urinary lysozyme with AMoL?
Bc. this enzyme found in greatest amount in monos
With AMoL, bone marrow shows some granulocytes, but majority composition is monoblasts, promonocytes, & monocytes.
* <___% granulocytes
20
AMoL:
MPO and SBB _________
+ / - (most frequently NEG.)
Are there Auer rods with AMoL?
Very rare Auer rods (most frequently NEG.)
AMoL:
PAS __________
positive
AMoL:
Both NSEs ________ (NBE ___)
positive
3+
Acute Erythroid leukemia
(AEL) only makes up ___% of AMLs.
3
-Can evolve further into AMLs
Only AML with marked erythroid precursor hyperplasia!!
Acute Erythroid leukemia
(AEL)***
Acute Erythroid leukemia
(AEL) is Frequently preceded by a ____________ syndrome.
myelodysplastic syndrome (MDS, aka. Refractory Anemia).
Acute Erythroid leukemia
(AEL) lab findings:
bone marrow shows ____________ (Atlas pp. 178-79) = abnormal proliferation of bizarre RBC precursors, with reverse M:E ratio due to huge # of abnormal erythroblasts,
& even a few ringed sideroblasts.
dyserythropoiesis
Peripheral blood findings with Acute Erythroid leukemia (AEL)?
nRBCs with mkd. aniso, poik. & schistocytosis (due to the dyserythropoiesis)
Acute Erythroid leukemia
(AEL) Lab Findings:
- Lots of myeloblasts
- Some abnormal _____________
megakaryocytes
Acute Erythroid leukemia
(AEL):
> ____% bizarre, multinucleated, megaloblastoid nRBCs!!
(with few ringed sideroblasts.)
50
Acute Erythroid leukemia
(AEL):
MPO/SBB ______. Why?
negative, Defect here is mostly dyserythropoiesis, not so much dysmyelo-
poiesis.
Acute Erythroid leukemia
(AEL):
- Both NSEs _______
- PAS __________
positive
positive
Acute Erythroid leukemia
(AEL):
Early, abn. erythroblasts are PAS + in “granular” or
“blocky” pattern. Later, abnormal erythroblasts + in
“_______” pattern.
diffuse
Acute Erythroid leukemia
(AEL):
Normal RBC precursors —> PAS ______
not PAS + at all!
Rarest form of AML!! (Makes up < 1% of AMLs.)
Acute Megakaryocytic/
Megakaryoblastic Leukemia (AMegL)
Acute Megakaryocytic/
Megakaryoblastic Leukemia (AMegL) is frequently associated with ________ syndrome.
Down’s Syndrome
Acute Megakaryocytic/
Megakaryoblastic Leukemia (AMegL):
Common leukemia symptoms + “dry tap” upon bone marrow aspiration due to ____________.
What other leukemia has “dry tap”?
myelofibrosis
Hairy Cell Leukemia
Acute Megakaryocytic/
Megakaryoblastic Leukemia (AMegL)
* Lab Finding: bone marrow shows primarily…
dysmegakaryopoiesis: ↑ #s of
megakaryocyte precursors, including megakaryoblasts,
atypical megakaryocytes (with “blebbing”), & giant plts. (Atlas pp. 182-83)
Acute Megakaryocytic/
Megakaryoblastic Leukemia (AMegL):
Few myeloblasts can look…
lymphoid or undifferen-tiated.
Does AMegL show dyserythropoises?
Little accompanying dyserythropoiesis
AMegL can be associated with t(____) & t(____).
t(3;21) & t(1;22)
AMegL:
AMP and SBB ______. Why?
negative, so few myeloid elements
AMegL:
NBE _____ but NAE ______. (unique to megakaryo-blasts)!
negative, positive
Acute Megakaryocytic/
Megakaryoblastic Leukemia (AMegL):
PAS ________
Plt. peroxidase _____
positive
postive
Acute Megakaryocytic/
Megakaryoblastic Leukemia (AMegL):
CD 41, 42, 61 ______
+/-
Acute Megakaryocytic/
Megakaryoblastic Leukemia (AMegL):
May plt.-specific receptors, such as _______________ + (for fibrinogen)
GPIIb/IIIa receptor
Acute Megakaryocytic/
Megakaryoblastic Leukemia (AMegL):
Acid phosphatase _____
What other leukemia is acid phosphatase +
positive
but this isn’t spe-cific for megakaryoblasts! In what
other specific leukemia was acid phos. stain pos.? —>
T-cell ALL
