Page 200 - Essential Haematology

186 / Chapter 13 Acute myeloid leukaemia

4 4
10 10
1000
800 3 3
10 10
SSC-H: Side Scatter 600 FL4-H: CD19 APC 10 2 FL4-H: CD33 APC 10 2

400
10 1 10 1
200
92.4
0 10 0 10 0
0 1 2 3 4 0 1 2 3 4
0 200 400 600 800 1000 10 10 10 10 10 10 10 10 10 10
FSC-H: Forward Scatter FL3-H: CD3 PerCP FL3-H: CD34 PerCP
4 4
10 10

3 3
10 10 Figure 13.6 FACS analysis of
FL4-H: CD33 APC 10 2 FL2-H: CD117 PE 10 2 AML – tumour cells are initially

gated on forward scatter (FSC)
1 1 versus side scatter (SSC). Further
10 10 analysis reveals (i) lack of
expression of lymphocyte markers
(CD3 and CD19), (ii) expression
10 0 10 0
0 1 2 3 4 0 1 2 3 4 of CD33 and (iii) CD117 as well
10 10 10 10 10 10 10 10 10 10
FL2-H: CD117 PE FL1-H: Anti-HLA-DR FITC as HLA-DR on a subset of cells.

15q22 17q12
1 2 3 4 5 6 3 4 5 6 7 8 9
PML BCR-1 RAR α

PML RAR α
BCR-1/L

Figure 13.7 Generation of the t(15; 17) translocation. The PML gene at 15q22 may break at one of three

different breakpoint cluster regions (BCR - 1, - 2 and - 3) and joins with exons 3 – 9 of the RAR α gene at 17q12.

Three different fusion mRNAs are generated (termed long (L), variable (V) or short (S)) and these give rise to
fusion proteins of different size. In this diagram only the long version resulting from a break at BCR - 1 is shown.

Promyelocytic leukaemia with the t(15; 17) Prognosis and t reatment s tratifi cation
translocation responds to treatment with high doses

of ATRA which causes differentiation of the abnor- The outcome for an individual patient with AML
mal promyelocytes and results in improved progno- will depend on a number of factors including age
sis. Interestingly, in rare variants of RAR α is fused and white cell count at presentation. However, the
to other genes and in these cases ATRA treatment genetic abnormalities in the tumour are the most
is not successful. important determinant.