Anaplastic lymphoma kinase

Anaplastic lymphoma kinase (ALL) is a protein that encodes a gene of the same name. Thus the term can refer to one or the other. As a protein it is found on the surface of cells, where it acts as a signal receptor (a receptor tyrosine kinase), meaning that it is an important regulator of many processes occurring within the cell.

[UPDATE: "anaplastic lymphoma kinase" is technically no longer in use as the name of the gene; it has been replaced by "anaplastic lymphoma receptor tyrosine kinase".]

While the ALK gene plays an important part in the life of the healthy cell, the gene has been implicated as an oncogene—cancer-causing—when it has been found to be amplified, rearranged, or mutated. Anaplastic lymphoma kinase is also one of the few tyrosine kinases that has been shown to have a role in the pathogenesis (medical terminology meaning the development of a disease) of some lymphomas.

Anaplastic lymphoma kinase in ALCL

Typically, cells express the ALK protein on their surfaces only in cells that are part of the development and maturity of the brain and central nervous system. Normal lymphoid cells, in persons of any age, do not express ALK.

The same is not true for some abnormal lymphoid cells. In fact, ALK expression can be found in over 60 percent of cases of the non-Hodgkin's lymphoma T-cell subtype anaplastic large cell lymphoma (ALCL), an extremely uncommon lymphoma, amounting to about 3 percent of all adult lymphomas. ALCL ALK+ (ALK positive) means that the disease is expressing the ALK protein on the surface of its cells. ALCL ALK- (ALK negative) means that the disease is not expressing the ALK protein. Whereas these two non-Hodgkin's lymphoma subtypes used to be considered two versions of the same disease, recent studies have shown that in fact they are fully separate disease entities with different treatment approaches and differing prognoses.

In fact, the prognosis differs drastically; ALK+ disease enjoys a very good prognosis when treated with CHOP chemotherapy—as many as 80 percent of all patients can look forward to a successful treatment course and a very long disease-free survival. On the other hand, as many as 70 percent of patients with ALK- disease are expected to relapse within five years of treatment.

Anaplastic lymphoma kinase in other cancers

The ALK is not only implicated in anaplastic large cell lymphoma. Recently it has been found to be responsible for a small percentage of neuroblastomas, a childhood form of brain cancer, an even smaller percentage of non small cell lung cancers, and some inflammatory myofibroblastic tumors.

Sources

• Savage KJ et al. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood. June 15, 2008 vol. 111 no. 12 5496-5504.
• Lymphoma Research Foundation, What you need to know about Anaplastic Large Cell Lymphoma
• GeneCards, ALK gene
• Kotuk JL, Aster JC. Molecular Biology of Anaplastic Lymphoma Kinase-Positive Anaplastic Large-Cell Lymphoma. JCO. September 1, 2002 vol. 20 no. 17 3691-3702
• NCBI: anaplastic lymphoma receptor tyrosine kinase.
• Chiarle R et al. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nature Reviews Cancer. January 2008; 8, 11-23
• Shaw AT, Solomon B. Targeting Anaplastic Lymphoma Kinase in Lung Cancer. Clin Cancer Res April 15, 2011 17;2081.