Prognostic markers for AML

Question 1

t(15;17) [both on q regions] => PML::RARa

a) Is this a Favourable/Intermediate/Adverse marker?
b) Mechanism of mutation i.e. effects

Answer 1

a) Favourable
b) PML on (15) > regulatory function
RARa on (17) > differential of tissues
=> PML::RARa fusion > enhanced affinity to sites on DNA, blocks transcription & differentiation of granulocytes => APL & DIC

Question 2

t(8;21) [both on q regions] RUNX1-RUNX1T1

a) Is this a Favourable/Intermediate/Adverse marker?
b) Mechanism of mutation i.e. effects

Answer 2

a) Favourable
b) RUNX1T1 on (8) > transcription factor (CBFa)
RUNX on (21) > transcription factor
=> RUNX1-RUNX1T1 fusion > altered transcription regulation of RUNX1 target genes => AML

Question 3

Inv(16) [pericentric- both sides of centromere] CBFbeta::MYH11

a) Is this a Favourable/Intermediate/Adverse marker?
b) Mechanism of mutation i.e. effects

Answer 3

a) Favourable
b) MYH11 on (16p13) > protein
CBFB on (16q22) > Transcription factor regulates haematopoeisis (RUNX gene)
=> CBFbeta::MYH11 fusion > product binds to RUNX1 = inhibit TF function in haematopoeisis => AML

Question 4

inv(3) [pericentric – both sides of centromere]

a) Is this a Favourable/Intermediate/Adverse marker?
b) Mechanism of mutation i.e. effects

Answer 4

a) Adverse
b) RPN1 (3q21)
MECOM part of MDS1/EV11 (3q26.2) => becomes upregulated by RPN => AML w/ multi-lineage dysplasia

Question 5

What classifies a Complex prognositic marker vs a monosomal karyotype?

Answer 5

Complex: ≥3 abnormalities
Monosomal: ≥2 autosomal monosomy (missing chrom. from 1-22) OR 1 autosomal monosomy w/ ≥1 structural abnormality

Question 6

Translocation mutations can be confirmed/detected using what type of probes? And what does the signals mean?

Answer 6

Dual fusion probe
Pos: R, G & 2x R-Y-G fusion
Neg: 2R, 2G

Question 7

(pericentric) Inversion mutations can be confirmed/detected using what type of probes? And what does the signals mean?

Answer 7

Break apart probe
Pos: R, G
Neg: R-Y-G fusion

Question 8

Complex AML and monosomal karyotype falls under the prognosic category of (favourable/intermediate/adverse)

Answer 8

Adverse = poor prognostic marker

Question 9

abn(17p)

a) Is this a Favourable/Intermediate/Adverse marker?
b) *Mechanism of mutation i.e. effects

Answer 9

a) Adverse

b) *

Question 10

Del(7q)

a) Is this a Favourable/Intermediate/Adverse marker?
b) *Mechanism of mutation i.e. effects

Answer 10

a) Adverse

b) *

Question 11

del(5q)

a) Is this a Favourable/Intermediate/Adverse marker?
b) *Mechanism of mutation i.e. effects

Answer 11

a) Adverse
b) 1. Gene dosage effect caused by multiple genes contained in the 5q region (genes involved in haematopoeisis) => AML OR
2. Deletions in 5q common in MDS

Question 12

t(9;11)(p;q)

a) Is this a Favourable/Intermediate/Adverse marker?
b) *Mechanism of mutation i.e. effects

Answer 12

a) Intermediate

b) *

Question 13

Trisomy 8

a) Is this a Favourable/Intermediate/Adverse marker?
b) *Mechanism of mutation i.e. effects

Answer 13

a) Intermediate

b) *