Biology of Disease

immature and mature myeloid cells within the bone marrow and spleen.

Chronic myelogenous leukemia usually follows a clinical pattern in which

there is a benign chronic phase, an accelerated phase and a blastic or blast

crisis phase. During the chronic phase there are few signs and symptoms and

many patients are asymptomatic. Patients may present with fatigue, anorexia

and weight loss, and splenomegaly, with the condition being revealed by a

routine blood count during the investigation of these symptoms. The blood

count shows a leukocytosis, that is, an increased number of leukocytes, ranging

from 10 q 109 to more than 500 q 109 cells dm–3. A blood smear also shows

large numbers of neutrophils and immature myelocytes. The Philadelphia

chromosome is present in 95% of cases (Section 17.4). Splenomegaly may

be present on examination. The presence of myeloblasts within a peripheral

blood smear indicates a worsening of the disease and progression into the

accelerated phase and the rapidly fatal blast crisis. This may take between

three and five years from diagnosis.

Two major treatments are available for CML. The first is stem cell

transplantation following radiation therapy to destroy the patient’s own

bone marrow (Chapter 6). The second is to use imanitib mesylate (Glivec)

together with IFN-A. Imanitib mesylate is an inhibitor of tyrosine kinase

that is administered orally. It is directed against the bcr-abl protein (Section

17.5) and is successful in inducing disease remission in approximately

90% of patients. However, the remainder are resistant, while up to 25% of

patients also develop resistance during treatment. Chemotherapy with

hydroxyurea may also be used. This is a temporary measure that reduces

the leukocyte count by suppressing the division of the malignant cells. The

effectiveness of treatment can be monitored by detecting the proportion of

cells with the Philadelphia translocation.

Acute myeloid (myeloblastic) leukemia

Acute myeloid leukemia (AML) is a rare disease that affects approximately

2000 adults, mostly over the age of 60 years, and 100 children annually in

the UK. The disease is characterized by the presence of immature myeloid

cells, or myeloblasts, in the blood, due to clonal proliferation of an aberrant

cell in the bone marrow. The cause of AML is unknown, though it has been

linked to exposure to industrial solvents. There is no genetic link and cases

are sporadic.

Acute myeloid leukemias are classified according to the type of cell which

is involved, using the FAB (French–American–British) classification (Table

17.12).

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Classification Description

M0 AML with minimal myeloid differentiation

M1 AML without maturation

M2 AML with maturation

M3 acute promyelocytic leukemia

M4 acute myelomonocytic leukemia

M5 acute monocytic/monoblastic leukemia

M6 acute erythroleukemia

M7 acute megakaryoblastic leukemia

Table 17.12FAB classification of acute myeloblastic leukemias