IBMS Congress

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The evolution of haematology

Session 3

Haematology

Prof Victor Hoffbrand, Royal Free, London

Over the last 50 years, major advances have occurred in the understanding the nature of all haematological diseases, in their classification, diagnosis and treatment.

In the 1960s research depended mainly on biochemical and basic immunological techniques. These led to the understanding of many red cell disorders e.g. enzyme defects and megaloblastic anaemia, although many protein and enzyme pathways e.g. in iron metabolism remained to be discovered. The classification of the haematological malignancies depended on morphology and cytochemistry. 

Monoclonal antibodies (Kohler, Milstein, 1975) are now a mainstay of diagnosis in all areas of haematology including blood transfusion, flow cytometry and immunohistology. They are used to detect minimal residual disease and have revealed early forms of B-lymphoproliferative diseases e.g. follicular lymphoma in-situ, monoclonal B-lymphocytosis, They are also used in therapy e.g. anti-CD20 in NHL and anti-C5 in PNH, anti-CD3 in stem cell transplantation.

The most spectacular advances, however, have come through the applications of cytogenetic, FISH and molecular genetic techniques e.g. Southern blotting (1975), PCR (1983). These led to the understanding of the genetic defects in the genetic disorders of haemoglobin and of coagulation factors and to the antenatal diagnosis of these diseases. More recently, genetic analysis has led to the recognition of previous unrecognised diseases, understanding the pathogenesis e.g. of childhood ALL, improved classification of the acute leukaemias, myelodysplasia and the lymphomas, and the detection of minimal residual disease. 

Therapy with recombinant growth factors e.g. erythropoietin, G-CSF and with replacement therapy for Gaucher disease and haemophilia, synthesized by recombinant DNA techniques has been introduced. Therapy targeted at the genetic defect has had spectacular success in CML; JAK2 inhibitors are now in trials in myeloproliferative disorders. 

New techniques of gene arrays are being used to detect multiple genetic defects eg in CLL on monoclonal antibody purified tumour cell populations

Current research using whole genome profiling is revealing the oncogenic changes that underlie the haematological malignancies.  Viral vectors encoding coagulation factors show promise for treatment of haemophilia and Factor IX Deficiency. Further molecular genetic research is likely to lead to improved classification of haematological diseases according to their underlying genetic defects and to improved therapy based on the knowledge of the ‘driver’ genetic defects.