About 25 percent of adults with ALL have a subtype called “Ph-positive ALL” (also known as “Ph+ ALL” or “Philadelphia chromosome-positive ALL”). The leukemia cells of these patients have the Philadelphia chromosome, which is formed by a translocation between parts of chromosomes 9 and 22. A piece of chromosome 9 breaks off and attaches to chromosome 22, and a piece of chromosome 22 similarly breaks off and attaches to chromosome 9. The abnormal chromosome 22 is known as the Philadelphia chromosome. This chromosomal alteration creates a fusion gene called BCR-ABL1. This gene produces a protein called a tyrosine kinase that causes the leukemia cells to grow and divide out of control.
Tyrosine Kinase Inhibitors
Tyrosine kinases are enzymes that are a part of many cell functions including cell signaling, growth and division. These enzymes may become too active in patients with an ALL subtype called Philadelphia chromosome-positive ALL (Ph+ ALL).
TKIs work to block these overactive enzymes and may stop cancer cells from growing. TKIs are pills taken by mouth. They are generally not used alone to treat ALL. Instead, they are added to other medications, such as a combination chemotherapy regimen. TKIs used in the treatment of Ph+ ALL include:
- Imatinib (Gleevec®)
- Dasatinib (Sprycel®)
- Ponatinib (Iclusig®)
- Bosutinib (Bosulif®)
- Nilotinib (Tasigna®)
Common side effects of TKIs include low blood counts, abnormal bleeding, pain, nausea and vomiting, diarrhea, fatigue, rashes, headaches, and pain in muscles, bones and joints. TKIs may also cause fluid to collect under the eyes, and in the hands, feet or lungs. Uncommon but serious side effects include a change in the rhythm of the heart, inflammation of the pancreas, blood vessel narrowing or blood clot formation.
Another 10 to 30 percent of adults who have ALL have a subtype known as “Philadelphia chromosome-like ALL” (Ph-like ALL). Unlike those with Ph+ ALL, who share a similar genetic mutation, patients with Ph-like ALL have a highly diverse range of genetic mutations that activate tyrosine kinase signaling. Researchers are working to understand better ways to identify these genetic mutations to determine whether specific TKIs may be effective.
For information about the drugs listed on this page, visit Drug Listings.
- Download or order The Leukemia & Lymphoma Society's free booklet, Acute Lymphoblastic Leukemia (ALL) in Adults.
- Chemotherapy and Other Drug Therapies