What is the Philadelphia Chromosome?
Sometimes our genetic material gets mixed up. Some genetic mutations occur when a piece of one chromosome breaks off, and it trades place with a piece of another chromosome. This is exactly what happens with the Philadelphia chromosome: a translocation, or swapping, of genetic information between human chromosomes 9 and 22. The shortened chromosome 22 then contains what is called the BCR-ABL gene. It causes the bone marrow to make an enzyme called tyrosine kinase. This enzyme in turn causes too many stem cells to become white blood cells – more than the body needs to fight off infections and other diseases.
The Philadelphia chromosome, sometimes abbreviated “Ph,” causes almost all cases of chronic myeloid leukemia (CML.) According to research recently conducted in Rome, the Philadelphia chromosome is also found in at least one quarter of adults who have acute lymphoblastic leukemia (ALL.) The Philadelphia chromosome is not inherited by a child whose parent has it.
Discovery and Treatment of Philadelphia Chromosome Positive Leukemia
The Philadelphia chromosome was discovered in 1960, well before the human genome was completely mapped. Knowing the chromosome causes leukemia, and understanding what it does in the body, has allowed scientists to develop a new generation of cancer fighting drugs. Called tyrosine-kinase inhibitors, these medicines are able to specifically target the cause of the cancer, instead of killing both healthy and malignant tissues in the body. The most commonly used tyrosine-kinase inhibitors are imatinib (Gleevec/Glivec) and dasatinib (Sprycel.)
According to the National Cancer Institute, treatment options for acute lymphoblastic leukemia include chemotherapy, radiation therapy and stem cell transplants. Treatment may also include biologic approaches that strengthen the immune system and help alleviate the side effects of treatments such as chemotherapy. When this type of leukemia is Philadelphia positive (Ph+ ALL) targeted therapy using tyrosine-kinase (tk) inhibitors is also an important option.
Treatment options for chronic myelogenous leukemia treatment include tyrosine-kinase inhibitors, chemotherapy and radiation, stem cell transplant with or without donor lymphocyte infusion, and biologic therapy using interferon. In some cases, the spleen may become very enlarged and may need to be surgically removed.
Stem Cell Transplants: Are You a Donor?
Chemotherapy alone is not enough for most people with Philadelphia positive leukemia. Targeted therapy using tyrosine-kinase inhibitors can improve survival rates, as can stem cell transplants received soon after the person achieves remission. While stem cells from a closely matched sibling are preferred the great majority of people who need a stem cell transplant depend on an anonymous donor. The difficulty of finding a matched donor for a person of African (or Asian) decent was brought to light through Montreal writer Emru Townsend’s personal fight with leukemia. Although there are over 12 million stem cell donors worldwide, the best match for a person with leukemia will usually come from someone of the same ethnicity. Unfortunately visible minorities tend to be under-represented on donor registries, making it even more difficult to find a matching stem cell donor for a person of colour.
A good match for stem cell donation relies on the donor and recipient having similar or identical human leukocyte antigen (HLA) profiles. One bone marrow donation FAQ explains there are some 150 billion different blood type and HLA combinations. While a person with a rare blood type could probably find a blood donor in a room of 100 people, it could take up to 50 stadiums of 20,000 people to find a stem cell donor match for some leukemia patients.
If you would like to help you can register as a stem cell donor by giving a cheek swab or blood sample. To learn more about stem cell donation, please visit one of the following organizations:
Be the Match (USA)
Anthony Nolan Trust (UK)
To learn more about ethnicity and stem cell donation for leukemia and related diseases, please visit Heal Emru. To learn how you can help Y!CN writer Rissa Watkins in her fight with leukemia, check out her Give Forward page.
“Adult acute lymphoblastic leukemia treatment” and “Chronic myelogenous leukemia treatment.” National Cancer Institute
“Definition of Philadelphia chromosome (Ph).” MedicineNet
Heal Emru stem cell donation awareness web site
“Stem cell transplantation.” Central European Leukemia Study Group
Antonella Vitale et al, “Advanced Philadelphia chromosome positive acute lymphoblastic leukemia patients relapsed after treatment with tyrosine-kinase inhibitors.” Haematologica