world cancer report - iarc

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