SM_269b: Acute Myeloid Leukemias Flashcards

1
Q

Describe clonal proliferation of immature myeloid precursors

A

Clonal proliferation of immature myeloid precursors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

AML has ___ blasts

A

AML has > 20% blasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

AML usually occurs at age ___

A

AML usually occurs at age 65

  • Slight male predominance
  • Poor survival
  • Rare in children but better survival
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Therapy-related AML occurs due to ___ and ___

A

Therapy-related AML occurs due to radiation / alkylating agents (cyclophosphamide, bendamustine) and topoisomerase-II inhibitors (etoposide, anthracyclines)

  • Radiation / alkylating agents (cyclophosphamide, bendamustine): del 5 and del 7, 5-10 years latency
  • Topoisomerase-II inhibitors (etoposide, anthracyclines): 11q23 translocation, 1-5 years after exposure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe AML clinical presentation

A

AML clinical presentation

  • General: fatigue, sweats, fever
  • Bone marrow failure
    • Anemia (pallor, fatigue, SOB)
    • Thrombocytopenia (bruising, bleeding)
    • Neutropenia (infection)
  • Extramedullary tissue infiltration: gingiva, skin, renal, lung, CNS, orbit
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe oncologic emergencies in AML clinical presentation

A

Oncologic emergencies in AML clinical presentation

  • Hyperleukocytosis (leukostasis) -> tumor lysis syndrome
    • Hyperuricemia, hyperkalemia, hypocalcemia
    • Acute renal failure
    • Cardiac arrhythmia
    • Hypoxia, dyspnea
    • Altered mental status
  • Coagulation abnormalities: disseminated intravascular coagulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

___, ___, ___, ___, and ___ are prognostic factors of AML

A

Age, performance status, history of prior cytotoxic therapy or MDS, cytogenetics and gene mutations, and leukocyte count at presentation are prognostic factors of AML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe use of bone marrow biopsy

A

Bone marrow biopsy

  • Aspirate smear and core biopsy for morphology
  • Flow cytometry
  • Cytogenetics + FISH
  • Molecular testing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

AML diagnosis requires ___ and ___

A

AML diagnosis requires ≥ 20% blasts in bone marrow or blood and evidence of myeloid differentiation

  • Auer rods
  • Cytochemistry: MPO+ or NSE+
  • Expression of myeloid-associated markers by immunophenotyping (flow cytometry)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Auer rods occur in ___

A

Auer rods occur in AML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe AML blast morphology

A

AML blast morphology

  • Myeloblasts w/ Auer rods
  • Monoblasts
  • Promonocytes
  • Promyelocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

This is ___

A

AML

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

AML cytochemistry involves ___ or ___

A

AML cytochemistry involves MPO+ myeloblasts or NSE+ monoblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe antigens expressed by myeloid cells

A

Antigens expressed by myeloid cells

  • Precursor markers: CD34, CD117
  • Granulocytic markers: CD13, CD33, MPO
  • Monocytic markers: CD14, CD64
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Morphological classification incorporates ___ and ___

A

Morphological classification incorporates type of cell and degree of maturity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe chromosomal abnormalities in AML

A

Chromosomal abnormalities in AML

  • In over half of adult AML
  • Most important predictor of outcome
  • Define diagnostic categories in WHO classification: AML with recurrent cytogenetic abnormalities, AML with myelodysplasia related changes
17
Q

Acute promyelocytic leukemia involves ___

A

Acute promyelocytic leukemia involves t(15;17) (q22;q12)

18
Q

Describe acute promyelocytic leukemia (APL) with t(15;17) (q22;12) / PML-RARA

A

Acute promyelocytic leukemia (APL) with t(15;17) (q22;12) / PML-RARA

  • Young patient with low blood counts and bleeding / bruising
  • Disseminated intravascular coagulopathy
  • t(15;17) (q22;a12), PML-RARA
  • Treated with all-trans-retinoic acid and arsenic trioxide
  • High cure rate (most curable AML)
19
Q

This is ___

A

APL with t(15;17) (q22;12)

20
Q

APL with t(15;17) (q22;a12) involves ___ that ___

A

APL with t(15;17) (q22;a12) involves PML-RARA fusion that blocks differentiation beyond promyelocyte stage

21
Q

In APL, when ____ and ____ bind to PML-RARA, there is no differentiation beyond promyelocyte stage

A

In APL, when ATRA and ATO bind to PML-RARA, there is no differentiation beyond promyelocyte stage

22
Q

Describe AML with t(18;21)

A

AML with t(18;21)

  • Molecular: RUNX1-RUNX1T1
  • Young adults
  • May present with myeloid sarcoma
  • Good prognosis
  • Kit mutation: 20-30% of cases (higher risk with relapse)
  • Morphology: large blasts with long sharp Auer rods
23
Q

Describe AML with inv(16)

A

AML with inv(16)

  • Molecular: CBFB-MYH11
  • Young adults
  • May present with myeloid sarcoma
  • Good prognosis
  • Kit mutation: 30-40% of cases (higher risk of relapse)
  • Morphology: atypical eosinophils
24
Q

Describe gene mutations in AML

A

Gene mutations in AML

  • 50% of AML have no defining chromosomal abnormality
  • Clinical utility of detecting mutations in AML: diagnosis (disease defining mutations), prognosis, targeted therapy, and disease monitoring
25
Q

AML involves ___ pathogenesis

A

AML involves two-hit pathogenesis

  • Class 1 (promote proliferation): RTK genes (FLT3, KIT, RAS)
  • Class 2 (impair differentiation): chromosomal abnormalities such as t(8;21) or inv (16), gene mutations (CZEBPA, RUNX1, MLL, NPM1)
26
Q

AML diagnostic mutations are ____, ____, and ____

A

AML diagnostic mutations are NPM1, CEBPA, and RUNX1

27
Q

AML prognostic mutations are ___ and ___

A

AML prognostic mutations are FLT3 and KIT

28
Q

Describe nucleophosmin 1 (NPM1)

A

Nucleophosmin 1 (NPM1)

  • Nucleolar phosphopotein
  • Shuttles basic proteins between nuclear and cytoplasmic compartments
  • Abnormal cytoplasmic localization of NPM1 protein led to discovery of mutations
29
Q

Describe clinical implications of NPM1 mutations

A

NPM1 mutations

  • Most common genetic aberration in AML
  • Often seen in AML with monocytic differentiation
  • More often in adults
  • Prognosis: favorable outcomes in absence of cytogenetic abnormalities and FLT3-ITD
  • Mutations stable over the course of disease: useful in monitoring disease and detection of MRD
30
Q

Describe CCAAT / enhanced binding protein alpha-CEBPA mutations

A

CCAAT / enhanced binding protein alpha-CEBPA mutations

  • 5-10% of AML
  • Confer favorable outcomes in cytogenetic negative AML
  • Two types of mutations: biallelic (dmCEBPA), monoallelic (smCEBPA)
31
Q

___ and NOT smCEBPA confer favorable outcomes in AML

A

dmCEBPA and NOT smCEBPA confer favorable outcomes in AML

32
Q

Describe FLT3 mutation clinical implications in AML

A

FLT3 mutation clinical implications in AML

  • Prognosis: FLT3-ITD confers worse outcomes, impact of FLT3-KD mutations remains controversial
  • Therapy: stem cell transplantation, tyrosine kinase inhibitors (midostaurin)
33
Q

Labeling AML with a single mutation is ____

A

Labeling AML with a single mutation is inadequate

  • Mutations do not occur in isolation: genetic complexity, integrated genomic profiling
  • AMLs are spatially and temporally heterogeneous: genetic heterogeneity and clonal evolution
34
Q

Describe AML treatment

A

AML treatment depends on type of leukemia, risk factors, and targetable mutations

  • General: induction chemo followed by post-remission chemo (consolidation) or hematopoietic stem cell transplantation
  • FLT3: midostaurin
  • IDH1: ivosidenib
  • IDH2: enasidenib