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FCPath(SA)Haem - HaemOnc > AML > Flashcards

AML Flashcards

AML

1
Q

AML favourable molecular genetics

A
  1. CBF Leuks - t(8;21) & inv 16
  2. NPM1 WITHOUT FLT3
  3. bZIP CEBPA
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2
Q

AML Intermediate risk molecular genetics

A
  1. NPM1 with FLT3
  2. t(9;11)
  3. Other cytogenetic abnormality
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3
Q

AML Unfavourable molecular genetics (7)

A
  1. Complex karyotype (>4 abnormality)
  2. Inv(3)
  3. t(6;9)
  4. KMT2A
  5. AML-MR
  6. TP53
  7. t(8;16)
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4
Q

APL genetics

A

t(15;17) PML::RARA

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5
Q

AML subtypes 2022 WHO classification

A
  1. AML with defining genetic abN
  2. AML MR
  3. AML with other defined genetic alterations
  4. AML defined by differentiation
  5. Myeloid sarcoma
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6
Q

Chemical exposure leading to AML or myelodysplasia

A

Benzene
Chlorambucil
Melphalan
(+RT)

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7
Q

Transient abnormal myelopoiesis (TAM) of Downs Syndrome

A

Blasts:
Undifferentiated/small Megs with blebbing/large megakaryoblasts.

IMPT:
Positive CD117
Variable CD34, CD36, CD42 and CD61
Aberrant expression of CD56 and CD7.

Trisomy 21
GATA1

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8
Q

What are the AML with defining genetic abN (6)(3)(2)

A

Translocations
2. PML::RARA t(15;17)
2. RUNX1::RUNX1T1 t(8;21)
3. CBFB::MYH11 inv16
4. DEK::NUP214 t(6;9)
5. RBM15::MRTFA t(1;22)
6. BCR::ABL1 t(9;22)

Rearrangements
1. KMT2A rearrangements (11q23)
2. MECOM “ (inv3)
3. NUP98 “ (11p15)

Mutations
1. NPM1 mutation
2. CEBPA mutation (biCEBPA and bZip)

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9
Q

What are some key morphologic

features of AML with t(8;21) ?

A

Blasts:
* Large
* Deep basophilic cytoplasm
* Azurophilic granules (pseudo-Chediak Higashi)
* Perinuclear hofs
* Single, long tapered Auer rods

Neutrophils:
* Variable dysplasia
* Hyposegmentation
* Abnormal cytoplasmic granulation ( homogeneous pink)

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10
Q

What is the immunophenotype of

AML with t(8;21) ?

A
  • Bright CD34, HLA-DR, MPO and CD13
  • Dim CD33
  • Maturation asynchrony (CD34 and CD15)
  • Other Key Markers positive:
    • CD19, Pax-5 and CD79a
    • TdT- weak expression
    • CD56
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11
Q

What are morphological features of AML with inv(16) or t(16;16) CBFB-MYH11 ?

A
  • Monocytic and granulocytic differentiation
  • Abnormal eosinophil component (M4 Eos)
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12
Q

What is an unusual cytochemistry finding

in AML with inv(16) ?

A
  • Chloracetate esterase
    • normally negative in normal eosinophils
    • faintly positive in the abnormal eosinophils in this AML
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13
Q

What is the immunophenotype of

AML with inv(16) ?

A
  • Complex immunophenotype with multiple blast populations
  • Immature blasts
    • CD34 and CD117 high expression
  • Granulocytic lineage
    • CD13, CD33, CD15, CD65 and MPO
  • Monocytic lineage
    • CD14, CD4, CD11b, CD11c, CD64, CD36 and lysozyme
  • Other markers often positive
    • CD2
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14
Q

What are the morphological variants of AML with t(15;17) PML::RARA ?

A

I. Hypergranular
* Densely packed granules and auer rods (faggot cells)
* Lower WCC

II. Microgranular
* Paucity of granules/Auer rods
* Higer WCC
* CD2 positive (association with FLT3)

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15
Q

What is the characteristic immunophenotype

of APL ?

A
  • Negative : CD34, HLA-DR
  • Positive: CD117, heterogenous CD13, bright CD33
  • Negative for granulocytic markers: CD15
  • Microgranular variant
    • some CD34 positivity and CD2 positive
  • CD56 - positive in 20% of cases (worse outcome)
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16
Q

Which variant APL translocations are
resistant to ATRA/ATO ?

A
  • ZBTB16-RARA (11q23)
  • STAT5B-RARA [t(17;17)]
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17
Q

What are the prognostic and predictive factors of APL ?

A
  • very sensitive to ATRA and arsenic trioxide
    • allows the cells to differentiate
  • best prognosis of all AML subtypes if treated appropriately
  • anthracycline is added for high risk patients
18
Q

Key morphologic
features of AML with t(6;9) / DEK::NUP214 ?

A

Multilineage dysplasia

19
Q

Key morphologic
features of AML with t(1;22) / RBM15::MRTFA ?

A

Similar to acute megakaryoblastic leukaemia (AML M7)

20
Q

What is the immunophenotype of the

blasts in AML with t(1;22) ?

A
  • Express one or more of the platelet glycoproteins:
    • CD41 (GP IIb)
    • CD61 (GP IIIa)
    • CD42b (GP Ib)
    • cytoplasmic staining more specific and sensitive for megakaryocytic differentiation
  • Positive for CD13 and CD33
  • Negative for:
    • CD45, CD34, and HLA-DR
    • MPO, lymphoid markers and TdT
21
Q

Key clincal and FBC
features of AML with t(1;22) / RBM15::MRTFA ?

A
  • HSM and cytopenias
  • EM disease
  • Liver fibrosis (Budd Chiari)
22
Q

Risk stratification of APL

A

SANZ Risk (WCC and Plt)

  • High: WCC > 10
  • Int: WCC < 10 & Plts < 40
  • Low: WCC < 10 & Plts > 40
23
Q

Treatment approach to APL

A

Induction:
* Low/Int Risk = ATRA+ATO / ATRA+Chemo (Dauno)
* High Risk = ATRA+ATO+Gemtuzumab / ATRA+Chemo (7+3)
* Week 4 BM = Cont until blasts < 5%

Consolidation

RQPCR:
Low Risk MRD Negative = FBC q3mo for 2-3yrs
High Risk MRD Negative = Maint Tx if ATRA+Chemo

MRD Positive = Try other induction strategy/HSCT

24
Q

APL Coagulopathy (Bleeding and Thrombosis)

A

Bleeding:
* > Fibrinolysis
* Annexin 2 (Receptor for Plasminogen and tPA)
* Granule content degrades vWF and fbg

Thrombosis:
* Endothelial disruption and Blast surface = > TF
* Cytokine release = > TF
* Cancer procoagulant (Activates F10)
* Death of blasts expose Phosphat. Serine

25
Q

Symptoms of Differentiation Syndrome

A
  • Fever
  • < BP
  • Wt gain
  • Pulmonary:
    • Dyspnoea
    • CXR opacities
    • Pleural/Pericardial effusion
  • AKI
26
Q

Treatment of Differentiation Syndrome

A
  • Dexa 10mg BD
  • If Severe - Stop ATRA/ATO & Dauno±Cytarabine or HU (< WCC)
27
Q

Molecular and IMPT of AML with t(9;22) BCR::ABL1

A
  • p210
  • Positive for CD7, CD19 and TdT
28
Q

DDx for AML with Dysplasia

A
  1. AML t(6;9)
  2. MECOM
  3. AML-MR
29
Q

DDx for AML with Monocytoid appearance (M4/M5)

A
  1. NPM1
  2. KMT2A (adults)
  3. APL (microgranular)
  4. NUP98
30
Q

DDx for AML with M7 fts

A
  1. t(1;22)
  2. NUP98
  3. MECOM
  4. KMT2A (kids)
  5. CBFa1::GLIS (RAM IMPT)
31
Q

DDx for Basophilia

A
  1. Acute basophilic leukaemia
  2. t(6;9)
  3. AML t(9;22)
  4. CML-BP
  5. Mast cell leukaemia
32
Q

WHO 2022 AML defined by morphology types

A

M0 (Min differentiation)
* 2+ Myeloid markers (CD13, 33 and 117)
* MPO Negative

M1 (Without Maturation)
* MPO Positive
* < 10% of BM cells are granulocytes

M2 (With Maturation)
* < 10% of BM cells are granulocytes
* < 20% Monos

Acute Basophilic Leukaemia
* Basophils and precursors 20-80%
* Metachromatic blasts on Tolidine Blue
* t (x;6) MYB::GATA1 (in male infants)
* IMPT: Positive for CD11b, 13, 33, 34, 38, 123 and 203

M4 (MyeloMonocytic)
* Granulocytes > 20% of BM cells
* Monos > 20% but < 80% of BM cells

M5 (Monocytic/Monoblastic)
* 80% + of leukaemic cells are monocytoid

M6 (Acute erythroblastic leukaemia)
* Blebs and vacuoles
* CD36, CD71 and CD117 (subset) Positive
* CD34 and HLA-DR Negative

M7 (Acute Megakaryoblastic Leukaemia)
* Adults (TP53, RB1, ASXL1 and DMT3A)
* Kids
* With DS (RUNX1 and GATA1)
* Without DS (CBFa2::GLIS2, RBM15::MRTFA, NUP::KDM5A, KMT2A)
* IMPT:
* Positive: CD36, CD41, CD42b, CD61, CD33, CD34 (half of cases) and CD4, CD7, CD56
* Negative: MPO
* RAM IMPT: Bright CD56, mod CD34 and variable CD117 - CFBa2::GLIS

33
Q

Diagnostic criteria for AML-MR

A

I. >20% Blasts

II. No previous:
* Cytotoxic chemo
* MPN
* AML with defining gentic abnormality
* MNGP

III. Hx of MDS/Overlap
or
IV. Defining cytogenetic/molecular abnormalities

34
Q

What are the defining cytogenetic abnormalities for AML-MR

A
  1. del5q
  2. del7q/mono7
  3. del11q
  4. del12p
  5. del13q/mono13
  6. del17p/iso17
35
Q

What are the defining molecular abnormalities for AML-MR

A
  1. ASXL1, BCOr, EZH2
  2. SF3B1, SRSF2
  3. STAG2
36
Q

What are dysplastic features in the BM

A

I. Granulocytes:
* Hypogranular
* Hypo/hypersegmented
* Pseudo Pelger-Huet

II. Megs
* MicroMegs
* Monolobated/hypolobated
* Loose nuclear fragments

III. Erythroid
* Megaloblastic changes
* Karyorrhexis
* Nuclear irregularity
* Multiple nuclei
* Cytoplasmic vacuoles
* Ring sideroblasts
* NOTE: AML M6 trumps AML-MR

37
Q

What are the AML with other defined genertic alterations?

A

I. RUNX1T3(CBFa2)::GLIS2 / inv16
* M7 - RAM IMPT

II. KAT6A::CREBBP / t(8;16)
* Erythrophagocytosis, Leukaemia cutis and DIC
* Monocytoid (Positive CD4, CD14)
* Positive for CD13, CD33, CD56, HLA-DR
* Negative for CD34 and CD117

III. FUS::ERG / t(16;21)
* Bad prognosis

IV. MNX1::ETV6 / t(7;12)

V. NPM1::MLF1 / t(3;5)

38
Q

AML with Mixed/Ambiguous Lineage classification WHO 2022

A

I. ALAL with defining genetic abN
* MPAL with BCR::ABL1
* MPAL with KMT2A
* Other:
* MPAL with ZNF384
* ALAL with BCL11B

II. ALAL IMPT defined
* MPAL, B/M
* MPAL, T/M
* MPAL, Rare
* ALAL, NOS
* Acute undifferentiated leukaemia

39
Q

What is Acute Undifferentiated Leuakemia

A
  • No lineage specific markers
  • Not > 1 maker for a lineage
  • 1 Myeloid marker (CD13, 33, 117)
  • Positive for CD34, HLA-DR and TdT
  • Variable expression of CD7 or CD56
40
Q

Lineage specific markers

A

I. B:
* Bright CD19 with 1+ (CD10, CD22, CD79a)
* Dim CD19 with 2+

II. T:
* c/sCD3

III. Myeloid:
* MPO or
* Mono 2+ (NSE, CD11c, CD14, CD64, lysozyme)

FCPath(SA)Haem - HaemOnc (20 decks)

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