Anaplastic lymphoma kinase (ALK)

ALK is  a receptor tyrosine kinase (RTK), which is a type of enzyme that is encoded by the ALK gene. Over 500 different kinases have been identified in humans, of which 58 are receptor tyrosine kinases.

Normal Function

ALK plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system through its signaling pathway.

Cancer Causing

The ALK gene can be oncogenic in two ways – first, by forming a fusion gene with any of several other genes, and second, with mutations of the actual DNA code for the gene itself.

Anaplastic large cell lymphoma (ALCL)

The fusion gene consisting of the ALK (anaplastic lymphoma kinase) gene and the nucleophosmin (NPM) gene is associated with approximately 60% of anaplastic large cell lymphomas (ALCLs).  Anaplastic large cell lymphoma (ALCL) is a rare type of aggressive T-cell lymphoma, comprising between 2.5% and 5% of all non-Hodgkin lymphomas (although it is much more common among children). (see article)   Approximately 50,000 cases of non-Hodgkin lymphoma are diagnosed annually in the United States. (see Article) Thus it appears that ALCls occur between 1,250 to 2,500 times a year in the United States.

Non-small cell lung cancer

The EML4-ALK fusion gene is responsible for approximately 3-8% of non-small cell lung cancer(NSCLC). The vast majority of cases are adenocarcinomas. Patients are aproximatly 10-15 years younger on average than other lung cancer patients. Patients are also significantly more likely to be non-smokers and somewhat more likely to be light former smokers.  Estimated to be 8-10,000 new ALK + patients in the United States each year and 40,000 patients worldwide.

Glioblastomas

About 17,000 new glioblastomas cases in the United States each year. They are the most frequent malignant brain tumors. (see Article) ALK is found to be overexpressed in many glioblastomas (see Article) Not clear exactly what percentage are ALK+ .

Neuroblastoma

Neuroblastoma is the most common solid tumor in childhood. An August 2010 review article said that “data provide a strong indication that ALK gain-of-function mutations underlie most cases of hereditary neuroblastoma.”  “In addition, ALK mutations and amplications were proven to play a role in more than 10% of sporadic neuroblastoma patients.” (See ArticleApproximately 500 cases of neuroblastoma are diagnosed annually in the United States. (See article)

 Inflamatory Myofibroblastic 

About 250 cases a year. About 60% have overexpression of ALK. (see Article)

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