Page 207 - Essential Haematology

Chapter 14 Chronic myeloid leukaemia / 193

(b)
(a)
I 2 3 XI
ABL1
Chromosome
9 I m-BCR M-BCR XI
BCR
1 2 3 4 5

(c) BCR ABL1
ABL1 22 2 3 9
Gene 5' 3'

BCR ABL1
Chromosome RNA 5' 3'
22
BCR
Ph'
CML Protein NH 2 COOH
Normal t(9;22) 210 kD

Figure 14.1 The Philadelphia chromosome. (a) There is translocation of part of the long arm of chromosome 22

to the long arm of chromosome 9 and reciprocal translocation of part of the long arm of chromosome 9 to
chromosome 22 (the Philadelphia chromosome). This reciprocal translocation brings most of the ABL gene into
the BCR region on chromosome 22 (and part of the BCR gene into juxtaposition with the remaining portion of
ABL on chromosome 9). (b) The breakpoint in ABL is between exons 1 and 2. The breakpoint in BCR is at one
of the two points in the major breakpoint cluster region (M - BCR) in chronic myeloid leukaemia (CML) or in some
cases of Ph + acute lymphoblastic leukaemia (ALL). (c) This results in a 210 - kDa fusion protein product derived
from the BCR - ABL fusion gene. In other cases of Ph + ALL, the breakpoint in BCR is at a minor breakpoint
cluster region (m - BCR) resulting in a smaller BCR - ABL fusion gene and a 190 - kDa protein. (Continued)

increased in survivors of the atom bomb exposures 6 Rare symptoms include visual disturbances and

in Japan. Its clinical features include the priapism.

following: 7 In up to 50% of cases the diagnosis is made

incidentally from a routine blood count.
1 Symptoms related to hypermetabolism (e.g.
weight loss, lassitude, anorexia or night sweats).
2 Splenomegaly is nearly always present and is fre- Laboratory fi ndings

quently massive. In some patients splenic enlarge-
9
ment is associated with considerable discomfort, 1 Leucocytosis is usually > 50 × 10 /L and some-
9
pain or indigestion. times > 500 × 10 /L (Fig. 14.2 ). A complete
3 Features of anaemia may include pallor, dysp- spectrum of myeloid cells is seen in the peripheral
noea and tachycardia. blood. The levels of neutrophils and myelocytes

4 Bruising, epistaxis, menorrhagia or haemorrhage exceed those of blast cells and promyelocytes
from other sites because of abnormal platelet (Fig. 14.3 ).
function. 2 Increased circulating basophils.

5 Gout or renal impairment caused by hyperuri- 3 Normochromic normocytic anaemia is usual.

caemia from excessive purine breakdown may be 4 Platelet count may be increased (most fre-
a problem. quently), normal or decreased.