Modern
chemotherapy of leukaemia was developed during the 1940-50s following the
observation that soldiers exposed to mustard gas during World War 1 suffered
from aplastic anaemia. In 1943, Louis Goodman et al. insightfully reasoned that
mustard gas related compounds could inadvertently be used to treat leukaemia
and lymphoma. Successful repression of lymphoma in a xenograft mouse model led
to a hurried search for related chemicals with anticancer activity culminatingin the first chemotherapeutic effort to tackle childhood leukaemia in 1948,using methotrexate.
Since then a myriad of new drugs with alternative
mechanisms of action have emerged, but common to many anti-leukaemia cell
toxins is their ability to induce bone marrow suppression. Aplastic anaemia
(AA) is a form of bone marrow failure in which the primary defect occurs at the
level of the haematological stem cell. AA is considered the paradigm of bone
marrow failure syndromes and will serve as such within the context of this
review. The disease is characterized by bone marrow hypocellularity,
pancytopenia and is frequently associated with malignant progression. AA can be
hereditary or acquired. Read more.................
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