Page 187 - Essential Haematology

Chapter 12 Haematological malignancy: management / 173

Purine synthesis Pyrimidine synthesis

6 mercaptopurine
Azathioprine
Methotrexate

Ribonucleotides

Hydroxyurea

Deoxyribonucleotides
Cytosine arabinoside
Fludarabine

Alkylating agents DNA
Anthracyclines
Etoposide
Bleomycin
ATRA
Demethylation agents
RNA

Asparaginase

Vinca alkaloids Protein
Imatinib
Bortezomib

Monoclonal antibodies Cell

Figure 12.5 The site of action of drugs used in the management of haemopoietic malignancies. ATRA, all - trans

retinoic acid.

reactive alkyl groups which make covalent bonds to 1 Inhibitors of de novo DNA synthesis. Hydroxyurea
molecules within the cell. These have a particular (hydroxycarbamide) is used widely in the treat-

affinity for purines and are thus able to cross - link ment of myeloproliferative disorders. It inhibits

DNA strands and impair DNA replication, result- the enzyme ribonucleotide reductase which con-
ing in a block at G 2 (see Fig. 1.8 ) and death of the verts ribonucleotides to deoxyribonucleotides.
cell by apoptosis (see Fig. 1.11 ). Bendamustine is a It is not thought to permanently damage DNA
unique drug in this class as it also appears to have and is used in non - malignant disorders such as
activity associated with purine analogue function. sickle cell anaemia (see p. 103 ).
Antimetabolites block metabolic pathways used 2 Folate antagonists , such as methotrexate (see Fig.

in DNA synthesis. There are four major groups: 5.5 ). Methotrexate is widely used alone or in