AML

Question 1

What is the incidence of AML

Answer 1

• Peaks infancy 12 per million

- Constant during childhood 5 per million

Question 2

Twin Concordance rates for AML

Answer 2

• Infant: 100% concordance
• 1-6: 10-20% concordance
• > 6 years: Minimal

Question 3

Major Leukemia Predisposition

Answer 3

• Bone Marrow failures: MDS, AML
• JMML- Noonan, NF1
• Down Syndrome
• Ataxia Telangiectasia
• Bloom Syndrome
• Li-Fraumeni syndrome

Question 4

Describe pathogenesis of Fanconi Anemia

Answer 4

Mutation in one or several components of FA/BRACA multi-protein complex involved in DNA repair resulting in chromosome instability

Question 5

Describe pathogenesis of dyskeratosis congenita

Answer 5

Mutation in one or several components of telomerase complex (DKC1(XR), TERC (AD), defective telomere maintenance

Question 6

Bone marrow failures presenting with Pancytopenia

Answer 6

• Fanconi Anemia

- Dyskeratosis congenita

Question 7

Diamond-Blackfan Anemia

Answer 7

Mutation of ribosomal protein genes.

Question 8

BMF syndromes presenting with Neutropenia

Answer 8

• Schwachman diamond syndrome

- Kostmann syndrome

Question 9

Schwachman-Diamond syndrome

Answer 9

SBDS mutations, affecting rRNA processing and 40s subunit biogenesis

Question 10

Kostman syndrome

Answer 10

Mutation in ELA, GF1 and HAX genes. Results in agranulocytosis and secondary activation of GCSF receptor leading to AML

Question 11

BMF syndromes presenting with thrombocytopenia

Answer 11

• Congenital Amegakaryocytic leukemia

- Familial platelet disorder with predisposition to AML

Question 12

Congenital amegakaryocytic thrombocytopenia

Answer 12

MPL mutation

Question 13

Familial platelet disorder with predisposition to AML

Answer 13

AML1 mutation

Question 14

What are the “ Big 4 “ recurrent genetic abnormalities in AML?

Answer 14

t(8;21), inv16; t(15;17); MLLr

Question 15

Characteristic mutations associated with MDS?

Answer 15

-7, del 5q,

Question 16

Characteristic chromosomal abnormalities of Alkylating agents?

Answer 16

• 7, del(7q), -5, de5(q)

- Long latency

Question 17

Characteristic chromosomal abnormalities of topoisomerase inhibitors/ anthracyclines ?

Answer 17

11q23

short latency

Question 18

Immunophenotype

Answer 18

Pan-myeloid: 13, 33, MPO
Monocytic: 11b, 14 
Erythroid: Glycophorin A ( 235a)
Megakaryocytic: 41a, 42, 61,  NO MPO
APL: HLA_DR neg CD 34 neg
t(8;21) often CD19+

Question 19

Name 2 leukemias of ambiguous lineage?

Answer 19

• Acute undifferentiated leukemia

- Mixed phenotype Acute Leukemia

Question 20

Adverse prognostic factors of AML

Answer 20

• Non-whites
• Under or over weight
• Pharmocogenomic
• Unfavorable cytogenetics
  
  • t-AML, MDS
  • 7, -5 and 3q
  • FLT3 ITD
  • Induction failure
  • MRD end of block 1 >0.01

Question 21

Favorable prognostic factors

Answer 21

Down syndrome related AML
APL with t(15;17)
Cytogenetics: inv 16, t(8;21)
Molecular: NPM1, CEBPA
MRD<0.01

Question 22

Indications for radiation for AML

Answer 22

• Emergent treatment for chloroma

Question 23

What are the 3 phases of CML

Answer 23

• Chronic phase
• Accelerated Phase
• Blast Crisis

Question 24

CML diagnosis

Answer 24

Demostrate p210 BCR-ABL fusion by PCR