MIDTERM LECTURE 2: ACUTE MYELOID LEUKEMIA Flashcards
most common type of leukemia in adults
AML
FAB classification is identified based on
morphology and cytochemistry
WHO classification is identified based on
molecular characterization and cytogenetics
General clinical presentation of AML
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
wbc count of px w/ AML
5-30x10^9/L
bleeding abnormalities in AML is associated with what disorder
disseminated intravascular coagulation (DIC)
clinical findings in AML
1) anemia
2) thrombocytopenia
3) neutropenia
4) pallor
5) fatigue
6) fever
7) bruising
8) bleeding
9) splenomegaly
anemia in AML is due to
overproduction of blast cells
neutropenia in AML is due to
blast cells tend to forget to mature
how many percentage of px w/ can be seen with splenomegaly
50%
abnormalities in laboratory results in AML
1) hyperuricemia
2) hyperphosphatemia
3) hypocalcemia
4) hypokalemia
cause of hyperuricemia in AML
caused by increased cellular turnover
cause of hyperphosphatemia
due to cell lysis
cause of hypocalcemia
hyperuricemia and hyperphosphatemia involves in bone destruction
group of metabolic complications that occurs in px with malignancy, with or without treatment
tumor lysis syndrome
tumor lysis syndrome is notable in what diseases
lymphoma and leukemia
tumor lysis syndrome is caused by
breakdown of the products of dying cancer cells
how does tumor lysis syndrome lead to renal failure
dying cancer cells products-> acute uric acid nephropathy-> renal failure
tumor lysis syndrome is characterized by
hyperkalemia
hyperphosphatemia
hyperuricemia
hyperuricosuria
subtypes of AML according to WHO classification
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
AML with recurrent genetic abnormalities
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
identify the mutation:
AML with t(8;21)(q22;q22.1)
RUNX1-RUNX1T1
identify the mutation:
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22)
CBFB-MYH11
identify the mutation:
AML with t(9;11)(p22;q23)
KMT21A (MLL)-MLLT3
identify the mutation:
AML with t(6;9)(p23;q34.1)
DEK-NUP214
identify the mutation:
AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)
GATA2, MECOM (RPN1-EVI1)
identify the mutation:
AML with t(1;22)(p13.3;q13.3)
RBM15-MKL1
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
AML RUNX1/RUNX1TI is found in how many percent of AML cases
5%
RUNX1/RUNX1T1 is diagnosed based on
genetic abnormality
RUNX1/RUNX1T1 clinical findings
-myeloblast w/ dysplastic cytoplasm
-auer rods
RUNX1/RUNX1T1 anomalies
-pseudo-Pelger-Huet cells
-hypogranulation
-eosinophilia
CBDB-MYH11 is also classified as what AML
Core-binding factors (CBF) AML
AML CBFB-MYH11 accounts for how many percentage of AML cases
5-8%
age of px that can develop Core-binding factors (CBF) AML
all ages
CBFB-MYH11 is predominant in what age
younger patients
diagnosis for CBFB-MYH11
genetic aberration
CBFB-MYH11 increases the incidence of what disease
extramedullary disease
common site for relapse in CBFB-MYH11
central nervous system
T or F:
remission is good in CBFB-MYH11
T
(but only 1/2 are cured)
identify the AML:
-characterized by differentiation block at the promyelocytic stage
APL w/ PML-RARA
percentage of PML-RARA in AML cases
5-10%
what age is PML-RARA predominant
young adults
diagnosis for PML-RARA
15;17 translocation
subtype of APL that accounts for 13-40% of APL cases and gives an appearance of having no granules
microgranular variant
how to differentiate APL with AML
1) auer rods
2) butterly/coin-on-coin nucleus
3) clinical presentation
treatment for APL w/ PML-RARA
1) All-trans-retinoic acid (ATRA)
2) Arsenic trioxide
what treatment of APL w/ PML-RARA is a vitamin A analogue and induces differentiation of malignant promyelocytes
ATRA
identify the AML:
-represents AML subgroups w/ 11q23 abnormalities
KMT2A (MLL)-MLLT3
what AML translocation is rare
AML with t(9;12)
characteristics of KMT2A (MLL)-MLLT3
1) large blast w/ abundant cytoplasm
2) fine nuclear chromatin
3) motile cells w/ pseudopodia
T or F:
KMT2A (MLL)-MLLT3 is frequently seen in adults
F
(frequent in children)
KMT2A (MLL)-MLLT3 is associated with what conditions
associated with gingival and skin involvement and DIC
identify the AML:
-20% blast cells
-multilineage dysplasia
-history of MDS/MPL
-MDS-associated cytogenetic abnormality
AML w/ myelodysplasia-related changes
AML w/ myelodysplasia-related changes should have the absence of what AML
AML w/ recurrent genetic abnormalities
AML w/ myelodysplasia-related changes primarily affects what age group
older adults
morphologic criteria for multilineage dysplasia
50% dysplasia in 2 lineages
significant dysplastic morphology of AML w/ myelodysplasia-related changes
1) pancytopenia w/ neutrophil hypo/hypergranulation
2) pseudo-Pelger-Huet cells
3) unsually segmented nuclei
describe the erythrocyte precursors of AML w/ myelodysplasia-related changes
1) vacuolated
2) karyorrhexis
3) megaloblastoid features
4) ring sideroblast
genetic findings of AML w/ myelodysplasia-related changes
complex karyotypes, -7/del(9q), and 5/del(5q)
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)
Classifications of AML w/ TMNS
1) therapy-related MDS
2) AML (t-AML)
3) myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN)
contributors for developing AML w/ T-MNs
1) alkylating agents
2) radiation
3) topoisomerase II
prognosis of AML w/ T-MNs
poor
what therapy-related neoplasm mutation behave more like the de novo counterparts
t(15;17) and inv(16)
identify the AML:
-occurrence of extramedullary proliferation of blast of one or more lineages
-disrupts the tissue architectures
myeloid sarcoma
commonly affected tissues in myeloid sarcoma
1) skin
2) GI tract
3) lymph nodes
10% of newborns that are present with abnormal myelopoiesis have what genetic abnormality
trisomy 21
identify the AML:
-spontaneous remission occurs within few months
-associated with GATA1 mutations
Myeloid proliferations related to down syndrome
Myeloid proliferations related to down syndrome has AML during the first 5 years of life increase by how much
fiftyfold
leukemia lineage of myeloid proliferations related to down syndrome
megakaryocytic lineage
treatment for myeloid proliferations related to down syndrome
chemotherapy
prognosis of myeloid proliferations related to down syndrome
young children: responds well
older children: do not fare
identify the AML:
-rare clinically aggressive tumor
-present skin lesions
-may progress involving peripheral blood and BM
Blastic Plasmacytoid Dendritic Cell Neoplasm
Blastic Plasmacytoid Dendritic Cell Neoplasm is derived from what precursors
plasmacytoid dendritic cell
AML category that do not fit into WHO subtypes
AML, not otherwise specified
WHO classification of AML not otherwise specified is identified according to
1) morphology
2) cytometric phenotypic
3) limited cytochemical reactions
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
AML, not otherwise specified requires how many percentage of blast to be diagnosed
20%
AML, not otherwise specified accounts for how many percent of AML cases
15%
FAB classification of AML with minimal differentiation
M0
blast description of AML with minimal differentiation
CD13+, CD33+, CD34+, CD117+
clinical presentation of AML with minimal differentiation
1) auer rods are absent
2) no clear evidence of cellular maturation
AML with minimal differentiation accounts how many percent of AML cases
5%
T or F:
AML with minimal differentiation is predominant in either infants or adults
T
cytochemical stain results of AML with minimal differentiation
1) MPO +
2) SBB +
3) NASDA +
4) ANAE -
5) ANBE -
FAB classification of AML without maturation
M1
blast description of AML without maturation
CD13+, CD33+
majority of the cases: CD117+, CD34
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
cytochemical stain results of acute myeloid leukemia without maturation
1) MPO +
2) SBB +
3) NASDA +
4) ANAE -
FAB classification of AML with maturation
M2
blast description of AML with maturation
1) >20% blast
2) at least 10% maturing cells of neutrophil lineage
3) <20% precursors with monocytic lineage
clinical presentation of AML with maturation
auer rods are often present
cytochemical stain results of acute myeloid leukemia with maturation
1) MPO +
2) SBB +
3) NASDA +
4) ANAE -
5) ANBE -
FAB classification of Acute myelomonocytic leukemia
M4
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
(+) myeloid antigens in M4
CD13, CD33
(+) monocytic antigens in M4
CD14,CD4,CD11b, CD11c, CD64
clinical presentation of AML with maturation
elevated WBC count
cytochemical staining results of acute myelomonocytic leukemia
1) MPO +
2) SBB +
3) NASDA +
4) ANAE +
5) ANBE +
FAB classification of Acute monoblastic and monocytic leukemias
M5a, M5b
Acute monoblastic and monocytic leukemias is aka
Schilling’s leukemia
80% of cells in Acute monoblastic and monocytic leukemia are from what origin
monocytic
evidence of maturation in monocytic leukemia
promonocytes that are blast equivalents
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
clinical presentation of Acute monoblastic and monocytic leukemias
1) extramedullary cutaneous, gingival infection
2) bleeding disorder present
3) nonspecific cytogenetic abnormalities are common
Acute monoblastic and monocytic leukemias accounts how many percent of AML cases
5%
T or F:
Acute monoblastic and monocytic leukemias is common in younger individuals
T
cytochemical staining results of Acute monoblastic and monocytic leukemias
1) MPO +
2) SBB +/-
3) NASDA -
4) ANAE +
5) ANBE +
FAB classification of pure erythroid leukemia
M6
pure erythroid leukemia is aka
Di Gugliielmo’s syndrome
blast description of pure erythroid leukemia
1) MDS with excess blast
2) 80% or more eythroid cell in BM
3) >30% are proerythroblast
significant dysplastic features of RBC precursors in M6
1) multinucleation
2) megaloblastoid asynchrony
3) vacuolization
clinical presentation of pure erythroid leukemia
1) complex arrangement of hypodiploid chromosome number are common
2) ring sideroblast,
3) Howell-Jolly body
what chromosomes are frequently affected in pure erythroid leukemia
chromosome 5 & 7
prognosis of pure erythroid leukemia
aggressive and rapid
cytochemical stain results of pure erythroid leukemia
1) MPO +/-
2) SBB +/-
3) NASDA +/-
4) ANAE -
4) ANBE -
FAB classification of acute megakaryocytic leukemia
M7
requirement for diagnosis of acute megakaryocytic leukemia
requires 20% blast, 50% megakaryocyte origin
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
how are megakaryoblasts identified in acute megakaryocytic leukemia
immunostaining
what are the antibodies are used in immunostaining for acute megakaryocytic leukemia
specific for cytoplasmic von Willebrand factor or platelet membrane antigens
platelet membrane antigens of acute megakaryocytic leukemia
CD41 (glycoprotein IIb)
CD42b (glycoprotein Ib)
CD61 (glycoprotein IIIa)
cytochemical stain results of acute megakaryocytic leukemia
1) MPO -
2) SBB -
3) NASDA -
4) ANAE -
5) ANBE -
identify the AML:
leukemia with no clear evidence differentiation along singe cell line
acute leukemia of ambiguous lineage (ALAL)
ALAL is commonly referred as
acute undifferentiated leukemia (AULs)
demonstrate multiplicity of antigens in which it is not possible to determine specific lineage
mixed phenotype acute leukemia (MPAL)
techniques used to identify AML subtype
1) flow cytometry
2) cytogenetic analysis
3) molecular testing
old yet important technique used to identify AML subtype
cytochemical stain
cytochemical stain result of ALL
1) MPO +
2) SBB -
3) NASDA -
4) ANBE -/+ (focal)
5) ANAE -‘+ (focal)
advantage of cytochemical stains
inexpensive
T or F:
lymphocyte exhibit MPO activity
F
leukemic myeloblast are usually (positive/negative) for MPO
positive
percentage of blast that shows MPO activity
80%
auer rods in leukemic blast and promyelocyte test strongly (positive/negative) for MPO
positive
maturing granulocyte test strongly (positive/negative) for MPO
positive
examples of negative MPO
lymphoblast in ALL
lymphoid cells
more sensitive cytochemical stain for early myeloid cells
SBB
granulocytes show (positive/negative result) in SBB
positive
why does the SBB stain becomes more intense as the granulocyte mature
increase in numbers of primary and secondary granules
monocytes show (positive/negative) stain in SBB
negative to weakly positive
lymphoid cells show (positive/negative) result in SBB
negative
how many enzymes of esterases are present in leukocytes
nine
esterases are used to differentiate what cells
myeloblasts and neutrophilic granulocytes from monocytic origin
commonly used substrate esters
a-naphtyl acetate and a-naphtyl butyrate
T or F:
ANAE and ANBE are specific
F
(both are nonspecific)
specific esterase reaction used
Naphthol AS-D chloroacetate
why is NASDA specific
only granulocytic cells stain
chloroacetate esterase is present in
primary granules of neutrophils
auer rods show (positive/negative) stain in SBB
positive
what does ANAE reveal
strong esterase activity in monocytes
strong esterase activity demonstrated in ANAE can be inhibited with
sodium fluoride
granulocyte show (positive/negative) stain in ANAE
negative
lymphoid cells show (positive/negative) stain in ANAE
negative
monocyte show (positive/negative) stain in ANBE
diffuse positive
T or F:
ANBE is more sensitive than ANAE
F
(less sensitive)
granulocytes show (positive/negative) stain in ANBE
negative
lymphoid cells show (positive/negative) stain in ANBE
negative (although a small positive dot may be seen)
T or F:
ANBE is more specific than ANAE
T
positive ANBE indicates what type of leukemia
ANBE