AML

Question 1

FAB Classification of AML

Answer 1

M0 - minimally differentiated

M1 - minimal maturation

M2 - with maturation

M3 - APML

M4 - myelomonocytic and M4-eo

M5 - monocytic

M6 - erythroblastic

M7 - megakaryocytic

Question 2

Features of M0

Answer 2

prominent nucleoli
no granules
no staining

Question 3

Features of M2

Answer 3

Auer rods

fine granules

Question 4

Features of M3

Answer 4

Faggot cells
fine chromatin
large nucleolus
basophilic cytoplasm

Question 5

Features of M4

Answer 5

granules stuck on top of nucleus

Question 6

General presentation in AML

Answer 6

BM FAILURE: anaemia, thrombocytopenia and neutropenia

Question 7

What are the chromosomal abnormalities in AML?

Answer 7

t(8;21)- RUNX1-RUNX1T1

t(15;17)- APML

inv(16) - CBFB-MYH11 [AML M4-eo]

Question 8

Good, intermediate and poor prognosis in AML

Answer 8

GOOD: t(8;21) , t(15;17), inv(16)

INTERMEDIATE: t(9;11); normal karyotype

POOR: inv(3); complex karyotype

Question 9

Presentation in APML

Answer 9

BLEEDING

• thrombocytopenia
• DIC (raised APTT, normal PT, low fibrinogen)

Question 10

APML morphology

Answer 10

• Faggot cells
• hypergranular
• many nucleoli

Question 11

APML chromosomal abnormality

Answer 11

t(15;17)

PML-RARA fusion protein - binds a NCoR-HD complex
this deacetylases histones so transcription is repressed

Give VITAMIN A and ATRA early.
– ATRA binds to RARA and releases the NCOR-HD complex so transcription is reactivated.

Question 12

AML definition

Answer 12

Clonal expansion of myeloid blasts cells where the %blasts in BM is >20% nucleated cells (Except APML)

Question 13

2-hit hypothesis is AML

Answer 13

Class I mutations: proliferative advantage

Class II mutations: impaired differentiation

RAS mutations gives poor prognosis

Question 14

RUNX1-RUNX1T1

Answer 14

t(8;21)

Normal RUNX1 activity is binding to DNA and causing transcription of many genes, mainly for myeloid differentiation
RUNX1-RUNX1T1 has a dominant negative effect on normal RUNX1
There is enhanced DNA binding and transcription of these genes

Need FISH for diagnosis

Good prognosis

Question 15

inv(16)

Answer 15

Paracentric inversion gives AML-M4eo

CBFB is brought adjacent to MYH11 gene, forming SMMHC and blocking myeloid differentiation

Diagnose with FISH

Question 16

PML-RARA overview/immunophenotype

Answer 16

t(15;17) - Single genetic alteration is enough to cause leukaemia.
Don’t need blasts 20%

Morphology: bilobed promyelocytes, faggott cells , granularity

Immunophenotype: Myeloid with HLA-DR -ve and CD34-