Philadelphia Chromosome Positive Leukaemia is a very rare condition, especially in childhood. It is five times more common in adults, than in children.

It is a high-risk abnormality and the only treatment that holds any promise of a cure, is a bone marrow transplant.

The Philadelphia Chromosome was first discovered in the cancer research laboratories of Philadelphia, U.S.A, and was thus named after the city. Nowell and Hungerford first described it in 1960.

In those days, little was known about the genetic material inside our cells, which instructs them to grow. Their complex nature could only be guessed at.

Shape and size could only identify chromosomes.

In the 1970’s, a technique was developed which helped identify individual chromosomes.

Then, 3 years later, it was shown that a "swapping of information" on two particular chromosomes – now known the Philadelphia translocation – played an important role in some leukaemia. (This was shown by Rowley.)

Research in the late 1980’s, developed new techniques allowing the chromosomes to be probed even further.

Chromosomal breakages in leukaemia coincided with genes involved in cell growth.

Translocation such as the Philadelphia, interfered with the instructions that tell cells to divide.

The ‘Philadelphia chromosome’ is an abnormal chromosome produced when part of the chromosomes 9 and 22 get ‘swapped over’ – exchanged or – translocated

There are 4 major forms of leukaemia:

• Chronic Lymphocytic
• Chronic Myeloid
• Acute Myeloid
• Acute Lymphoblastic

   

• Philadelphia is most strongly associated with Chronic Myeloid, but it sometimes appears to cause a ‘mixture’ of the leukaemia's, with no border line between them.

   

Philadelphia was the first genetic abnormality consistently associated with a particular form of cancer.

The translocation between chromosomes 9 and 22 creates a leukaemia specific gene, which makes cells resist treatment.

Chromosome abnormalities in blood cells of patients with leukaemia, are VISIBLSE signs of genetic changes, which convert normal into malignant cells.

The cause of Philadelphia’s translocation, or swapping over, is not known, but the ABNORMAL HYBRID GENE created, leads to the production of a novel protein, not normally found in the cell. This protein prevents normal cell development and growth, thus leading to leukaemia.

The Philadelphia chromosome creates a new leukaemia gene.

These abnormal chromosomes are only found in the leukaemia cells. All the other cells of the patient have normal chromosomes.

It is not known that a particular gene, termed the BCR/ABL gene, located on the Philadelphia chromosome, is abnormal, but why it is first generated is, as yet unknown.

Chromosome changes are a fundamental feature of leukaemia. They result in the creation of ABERRENT LEUKAEMIA – SPECIFIC GENES. The identification of these genes is the first step towards targeted therapy, i.e. being able to knock out the abnormal gene, or gene products, without risking widespread damage to the healthy tissue of the patient.

A number of new approaches have been developed in the laboratory. The abnormal leukaemia – specific proteins, produced by translocation, can be switched off by drugs, or by using a potentially, very important new approach called ANTISENSE treatment.

ANTISENSE molecules consist of small DNA strands that prevent abnormal proteins from being produced, which caused uncontrolled cell growth

These work in the laboratory, but further development is needed before they can be used on patients.

At present a bone marrow transplant is the only treatment holding any hope of a cure, but a great deal of research is going forward.

Cytogenetic / molecular is now being done in British laboratories, by such as Professor Tony Whetton, Professor of cell biology, who works with Dr Guy Lucas and colleagues, at Manchester Royal Infirmary, Manchester, and also by Emeritus Professor of Cytogenetics, Lorna Secker – Walker and Dr Christine J Harrison, Senior Lecturer in Cytogenetics, and colleagues at the Cytogenetics laboratory, the royal free hospital school of medicine, London.

The science of molecular biology, used in Cytogenetic research groups has led to a greater understanding of the molecular basis of disease, especially cancer.

All such laboratory studies are aimed at understanding how the abnormal genes and proteins cause leukaemia, and achieve a deeper understanding of the leukaemia cell.

This would lead to developing new drugs to reserve the process, hopefully with few, or no, side effects.

The Cytogenetics Department at the Royal free Hospital in London is researching into these genetic changes which convert a normal cell into malignant one.

Dr Christine Harrison oversees the unique Karyotype Database, which is the largest of its kind in the world, and hold information on chromosome changes in more than 2000 patients with Acute Lymphoblastic leukaemia.