world cancer report - iarc
world cancer report - iarc
world cancer report - iarc
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A B<br />
Fig. 5.111 (A) Bone marrow smear from a patient with acute lymphoblastic leukaemia. (B) Precursor B<br />
lymphoblastic leukaemia. This bone marrow smear shows several lymphoblasts with a high nuclear cytoplasmic<br />
ratio and variably condensed nuclear chromatin.<br />
ly accumulate in the bone marrow, ultimately<br />
replacing most of the normal cells<br />
and circulate in the peripheral blood. As<br />
already noted, leukaemias are categorized<br />
in relation to clinical course and cell<br />
lineage. In addition, reference may be<br />
made to the morphology, degree of differentiation,<br />
immuno-phenotype and<br />
genetic character of the malignant cell<br />
population [5].<br />
Acute lymphoblastic leukaemia (Fig. 5.111<br />
A) is characterized by lymphoblasts, most<br />
often of B-cell phenotype (about 80% of<br />
e1<br />
e1a2<br />
b2a2<br />
b3a2<br />
e19a2<br />
8605Met<br />
BCR-ABL<br />
both childhood and adult disease), and distinguished<br />
from lymphomas which involve<br />
more mature lymphoid cells and primarily<br />
inhabit lymph nodes and spleen. Precursor<br />
B-lineage blasts (Fig. 5.111B) exhibit a<br />
range of cytogenetic abnormalities. The<br />
t(9;22) translocation, which results in<br />
fusion of the “breakpoint cluster region”<br />
BCR on chromosome 22 and the cytoplasmic<br />
tyrosine kinase ABL on chromosome<br />
9, is associated with poor prognosis. B-lineage<br />
blasts express surface antigens such<br />
as CD10, CD19 and CD22 [6]. Precursor<br />
Fig. 5.112 Schematic representation of the disruption of the ABL and BCR genes in the t(9;22)(q34;21)<br />
chromosomal abnormality found in chronic myeloid leukaemia, which results in the formation of oncogenic<br />
BCR-ABL fusion genes. Segments of DNA which are transcribed to form the protein (exons) are<br />
labelled a, b and e. Arrows mark the breakage points.<br />
244 Human <strong>cancer</strong>s by organ site<br />
ABL<br />
1b 1a a2a3 a11<br />
e1’ e2’ BCR e6 b2 b3 e19<br />
T-cell phenotypes, expressing CD2, CD3,<br />
CD5 and CD7 surface antigens, make up<br />
15-20% of acute lymphoblastic leukaemia<br />
cases.<br />
Acute myeloid leukaemia (Fig. 5.113) is a<br />
clonal expansion of myeloid blasts in bone<br />
marrow, blood or other tissue [5]. The disease<br />
is heterogeneous and consists of several<br />
subtypes, which can be identified by<br />
karyotype [7]. Approximately 20% of<br />
patients have favourable cytogenetic<br />
abnormalities, including t(8;21), inv(16)<br />
and t(15;17). These types are uniformly<br />
distributed across age groups, suggesting<br />
a distinct etiologic agent. Approximately<br />
30% (predominantly patients over the age<br />
of 50, with a progressive increase in incidence<br />
with age) have unfavourable cytogenetic<br />
abnormalities, which include deletions<br />
of the long arm of chromosome 5 or<br />
7 or trisomy of chromosome 8.<br />
Approximately half have diploid cytogenetics<br />
and an intermediate prognosis. A significant<br />
fraction of the favourable cytogenetic<br />
group and a small fraction of the<br />
diploid group can be cured with combination<br />
chemotherapy. One subtype, acute<br />
promyelocytic leukaemia, is characterized<br />
by t(15;17) (Fig. 5.114, 5.116). The break<br />
point on chromosome 17 occurs within the<br />
gene for an all-trans-retinoic acid receptor<br />
(RARα) and generates the fusion gene<br />
PML-RARα on the derivative chromosome<br />
15 [8].<br />
Chronic myelogenous leukaemia (Fig.<br />
5.117) originates in an abnormal pluripotent<br />
bone marrow stem cell [5,9]. The disease<br />
has a cytogenetic hallmark, the<br />
Philadelphia chromosome, namely t(9;22)<br />
(Fig. 5.115). This translocation relocates<br />
the C-ABL proto-oncogene from chromosome<br />
9 to the breakpoint cluster region on<br />
chromosome 22 to form a new hybrid BCR-<br />
ABL oncogene. The BCR-ABL transcript is<br />
present in over 95% of chronic myelogenous<br />
leukaemia cases, and encodes a<br />
novel tyrosine kinase that is involved in<br />
pathogenesis, possibly by perturbing apoptosis.<br />
Chronic lymphocytic leukaemia is now<br />
recognized as being the same disease<br />
entity as small cell lymphoma, being a<br />
neoplasm of monomorphic small, round<br />
B-lymphocytes in the peripheral blood,