AML Flashcards
▪ otherwise known as Acute Non-Lymphocytic Leukemia (ANLL)
ACUTE MYELOCYTIC LEUKEMIA (AML)
▪ progressive, malignant disease affecting stem (precursor) cells
ACUTE MYELOCYTIC LEUKEMIA (AML)
▪ a stem cell disorder with predominance of blast cells (> 20%) in the blood or marrow
ACUTE MYELOCYTIC LEUKEMIA (AML)
• blast cells: immature due to
1) genetic mutation or 2) induced by radiation, virus, chemical exposure
partially differentiated or undifferentiated cells
• blast cells
▪ may resemble [?] at presentation due to ↑WBC counts (w/ fever and weakness) → [?] → [?]
acute infection
pancytopenia
death
(leads to abnormal bleeding; lack of resistance to infection; abnormal proliferates = normal decreases)
pancytopenia
▪ affects all ages, but increases with older age (> 60 years = disease of adulthood); newborns (pre-mature leukemic development)
ACUTE MYELOCYTIC LEUKEMIA (AML)
▪ also the most common form of acute leukemia during the first few months of life
ACUTE MYELOCYTIC LEUKEMIA (AML)
tested for the identification of AML stage or classification using stains and CD markers
• Myeloperoxidase (MPO)
• CD13
• CD33
• CD117
• CD14
• CD64
• first stage; large
primitive myeloblasts
• usually stained with MPO
primitive myeloblasts
• detected with CD13, CD33, and CD117 (more specific than staining/no staining capability; identification via CD markers/immunology)
primitive myeloblasts
• usually stained with MPO, Sudan Black B (SBB), Chloroacetate Esterase (CAE)
more mature blasts (2-3 stages)
AML ETIOLOGY
- RADIATION
- GENETICS
- CHEMICALS
▪ linked to an increase incidence of leukemia (aggravates leukemic conditions)
- RADIATION
Chromosomal defects
• aneuploidy
• breakage and rearrangement
- unstable chromosomes bound to be modified or rearranged
• breakage and rearrangement
- (e.g., Fanconi Syndrome, Bloom Syndrome, Ph1 chromosome)
• breakage and rearrangement
- extra or missing chromosome
• aneuploidy
- (e.g., Trisomy 21 or Down Syndrome)
• aneuploidy
- CHEMICALS
a. Leukomogen
b. Benzene
suppress the bone marrow and eventually causes aplasia
Leukomogen
(inhibition of production of blood cells in the bm = [?]; disease in which the red bone marrow disappears and consequently ceases to produce red blood cells, white blood cells and platelets)
balstic aplasia
Leukomogen proposed (still controversial; not evidential but linked to leukemia):
- chloramphenicol
- phenylbutazone
- arsenic-containing compounds
- sulfonamides
- insecticides
: only proven chemical known to cause cancer
Benzene
▪ not conclusive/proven to humans but linked like the chemical etiology
- VIRUSES
: • most common class of tumor associated with animal leukemia and lymphoma
▪ Type C RNA viruses
: • carry genes responsible for the induction of cancer
▪ Retroviruses (e.g., HIV)
• activates our proto-oncogene to oncogene which causes or induces cancer cells
▪ Retroviruses (e.g., HIV)
AML with minimal differentiation/ Undifferentiated leukemia
M0
(similar to Undifferentiated MDS; general features: myelocytic and monocytic origin)
M0
AML without maturation
M1
▪ myelocytic origin
M1
M2
M3
▪ > 30% myeloblast in BM
M1
▪ + Auer rods (fused primary granules; spindle-shaped, redpurple)
M1
M2
AML with maturation
M2
Myeloblast + Mature cells
M2
▪ myelocytic origin
M2
▪ > 30% myeloblast with > 10% granulocytic component
M2
▪ + Auer rods
M1
M2
→ t(8q;21)
M2
Acute Promyelocytic Leukemia /Hypergranular Promyelocytic Leukemia
M3
→ t(15;17)
M3
Lesser blast (2nd stage)
M3
▪ myelocytic origin
M3
▪ with heavy granulation
M3
▪ many Auer rods in bundles called “faggot cells”
M3
▪ nuclear shape: bilobed or reniform (kidney-shaped)
M3
▪ associated with DIC
M3
M3 Coagulation tests/blood findings:
• prolonged PT, APTT, TCT
• ↓fibrinogen, platelet, AT-III
• ↑FSP, fibrin monomers
• (+) D-dimer
Acute Myelomonocytic Leukemia
M4
→ inv(16) subclass M4e
M4
▪ > 20% of PB WBCs are monocytes or monocytic precursors (promonocytes)
M4
▪ > 30% blasts
M4
▪ > 20% granulocytes
M4
▪ associated with CNS involvement or tissue infiltration (capable of infiltrating tissue barriers on the brain)
M4
▪ increased lysozyme
M4
Acute Monocytic Leukemia
M5
Schilling’s Leukemia
M5
→ t(9;11)
M5
▪ > 80% of BM elements are of monocytic series
M5
▪ increased lysozyme
M5
▪ associated with CNS involvement
M5
• poorly differentiated monocytic leukemia (nonspecific cell location; due to the presence of promonocyte and mature monocyte in both PB and BM)
M5a
• predominant cell: promonocyte (immature) in BM and PB
M5a
• M5a distinguishing morphologic features:
- lacy chromatin in the nucleus (normal)
- cerebriform shape nucleus (brain-like structure)
well differentiated (more mature seen in PB)
M5b
• more of promonocytes (BM) and monocytes (PB)
M5b
Naegeli monocytic Leukemia
M4
Erythroleukemia
M6
Erythremic Myelosis
M6
DiGuglielmo Disease (common name)
M6
Pure Erythroid Leukemia
M6
▪ with neoplastic myeloblasts and erythroblasts
M6
▪ > 50% are erythroid cells in all stages of maturation in PB
M6
▪ > 30% blasts in PB (acute)
M6
▪ dyserythropoiesis (presence of erythroblasts, nuclear fragments, N:C asynchrony or megaloblastic changes, and normoblastosis)
M6
• normoblastosis: increased nucleated RBCs in peripheral blood (erythroblast)
M6
▪ Stains (+): Periodic Acid Schiff (PAS)
M6
Acute Megakaryocytic Leukemia
M7
→ ch21 abnormality
M7
▪ predominantly megakaryoblasts (≥30%)
M7
▪ > 30% myeloblasts
M1
M2
M7
▪ myelosclerosis
M7
• sclerosis of the bone marrow
M7
• obliteration of the marrow cavity by small spicules of bone
M7
• irregularly thickened bony trabeculae
M7
• proliferation of fibroblastic cells (build-up of fibrous CT) in the bone marrow (affecting blood production) associated with splenomegaly and enlargement of liver
M7
▪ Stains (-): SBB and Peroxidase
M7
M1, M2, M3 STAINS
▪ SBB
▪ Peroxidase (MPO)
▪ a-Naphthol chloroacetate esterase (ANCAE)
M4 STAINS
▪ SBB*
▪ PAS
▪ Peroxidase
▪ a-Naphthol chloroacetate esterase (ANCAE)
▪ a-Naphthyl butyrate (ANB) and acetate esterase
M5 STAINS
▪ PAS
▪ a-Naphthyl acetate esterase
▪ a-Naphthyl butyrate esterase (ANB)
▪ ANCAE
M6 STAINS
▪ PAS
▪ a-Naphthyl acetate esterase
▪ a-Naphthyl butyrate esterase
▪ a-Naphthol chloroacetate esterase (ANCAE)
M7 STAINS
▪ Acid phosphatase
▪ PAS
▪ a-Naphthol chloroacetate esterase (ANCAE)
WHO Classification - Main Categories of AML
- AML with recurrent cytogenetic abnormalities
- AML with multilineage dysplasia
- AML, Therapy related
- AML, Not otherwise specified (subclassified by morphology and immunophenotype).
AML with t(8;21) FAB:
M2
AML with inv(16) FAB:
M4e
APL with t(15;17) FAB:
M3
AML with t(9;11) FAB:
M5a
AML with t(1;22;21) FAB:
M7
▪ ≥20% blasts
AML with t(8;21)
▪ ≥10% maturing granulocytes
AML with t(8;21)
▪ Auer rods
AML with t(8;21)
APL with t(15;17)
▪ dysplasia
AML with t(8;21)
▪ abnormal granules
AML with t(8;21)
▪ Blasts with both monocytic and neutrophilic differentiation
AML with inv(16)
▪ increased eosinophils/immature eosinophils
AML with inv(16)
▪ Promyelocytes with azurophilic granules
APL with t(15;17)
▪ Monoblasts and promonocytes predominate
AML with t(9;11)
▪ Multilineage dysplasia
AML, therapy related
▪ RS
AML, therapy related
▪ increased basophils
AML, therapy related
▪ Any morphology may be seen but myelomonocytic is most common
AML with t(6;9)
▪ Any morphology may be seen except APL
AML with inv(3) or t(3;3)
▪ Megakaryoblastic morphology with small and large megakaryocytes
AML with t(1;22;21) FAB: M7
▪ Any
AML with FLT3 mutation/duplication
▪ Myelomonocytic and monocytic features
AML with NPM1 mutation
▪ Variable, generally similar to less differentiated AMLs in FAB scheme (M1, 2)
AML with CEBPA mutation
AML
Acute myeloid leukemia
APL
acute promyelocytic leukemia
ATRA
all-trans retinoic acid
PML
promyelocytic leukemia
RARα
retinoid acid receptor gene-α
CD13, CD33, CD117, CD19, CD34
AML with t(8;21)
CD13, CD33, CD14, CD4, CD64
AML with inv(16)
CD13, CD33, CD2, ± CD117
APL with t(15;17)
CD33, CD65, CD4, HLADR
AML with t(9;11)
CD13, CD33, CD34, ± CD56, CD57
AML, therapy related
CD13, CD33, CD38, HLADR, CD117
AML with t(6;9)
CD13, CD33, HLADR, CD34, CD38
AML with inv(3) or t(3;3)
CD41, CD61, ± CD13, CD33
AML with t(1;22;21)
CD13, CD33, CD34 is negative
AML with NPM1 mutation
CD13, CD33, CD65, CD11b, CD15
AML with CEBPA mutation
t(8;21)(q22;q22)
AML with t(8;21)
AML1/ETO
AML with t(8;21)
More favorable
AML with t(8;21)
AML with inv(16)
AML with CEBPA mutation
inv(16)(p13;q22)
AML with inv(16)
t(16;16)(p13;q22)
AML with inv(16)
More favorable if responsive to ATRA
APL with t(15;17)
Inc px survival upon treatment
ATRA
t(15;17)(q22;q12)
APL with t(15;17)
PML/RARα
APL with t(15;17)
Variants all involve 17q12
APL with t(15;17)
t(9;11)(p22;q23)
AML with t(9;11)
MLLT3-MLL
AML with t(9;11)
Intermediate
AML with t(9;11)
11q23 abnormality seen with topoisomerase II inhibitor–associated AML
AML, therapy related
Less favorable
AML, therapy related
AML with t(6;9)
AML with inv(3) or t(3;3)
AML with t(1;22;21)
AML with FLT3 mutation/duplication
Median survival: < 3 years
AML, therapy related
More favorable in absence of FLT3
AML with NPM1 mutation
NPM1 mutation
AML with NPM1 mutation
cytoplasmic expression
AML with NPM1 mutation
DEK-NUP214
AML with t(6;9)
t(6;9) (p23;q35)
AML with t(6;9)
Inv(3)(q21;q26.2)
AML with inv(3) or t(3;3)
t(3;3)(q21;q26.2)
AML with inv(3) or t(3;3)
RPN1- EV11
AML with inv(3) or t(3;3)
t(1;22)(p13;q13)
AML with t(1;22;21)
RBM15-MKL1
AML with t(1;22;21)
t(6;9)(p23;q34)
AML with FLT3 mutation/duplication
t(15;17)(q22;q12) or normal
AML with FLT3 mutation/duplication
CEBPA mutation
AML with CEBPA mutation
