Anaplastic lymphoma kinase (ALK)

Anaplastic lymphoma kinase is a receptor tyrosine kinase expressed in the CNS, small intestine, and testicle.

A member of the insulin receptor family of receptor tyrosine kinases.

Encoded on the ALK gene located on chromosome 2p23.

The ALK gene chromosomal rearrangements are highly sensitive to small molecule ALK tyrosine kinase inhibitors.

Approximately 5% of patients with non-small cell lung cancer have a rearrangement in the gene for anaplastic lymphoma kinase (ALK) an oncogenetic fusion protein.

Normally expressed in the CNS, small intestine, and testes.

Function of the ALK gene is unknown.

Anaplastic lymphoma kinase gene mutations or translocations had been found in anaplastic large cell lymphoma, neuroblastoma, inflammatory myofibroblastic tumor and non-small cell lung cancers.

A chromosomal translocation between chromosomes 2 and 5.

Overexpression of the ALK protein is a critical component in carcinogenesis of some lymphoma subtypes.

In a small proportion of lung cancer patients ALK rearrangements are present and is a result of a small inversion within chromosome 2p, leading to a fusion of a portion of the EML4 gene with exons 20 through 29 of ALK.

Aberrant activation seen in anaplastic B cell non-Hodgkin’s lymphoma which is due to chromosomal translocation of ALK to create a fusion gene with partners such as nucleoplasmin (NPM).

ALK cancer associated fusion genes preserve the C-terminal kinase domain of ALK and juxtapose this with upstream components of the partner gene..

90% of ALK positive lung cancer patients have never smoked or are light smokers.

ALK positive lung cancer patients do not overlap with the EGFR mutation, and patients typically have either ALK rearrangement or EFGR mutation, but not both.

ALK Positive lung cancer patients are on the average 10 to 15 years younger than those without such a rearrangement and have a median age of about 50 years.

Adenocarcinomas of the lung rather than squamous cell carcinoma is associated with ALK rearrangements.

The EML4-ALK fusion gene encodes a potent oncogenic fusion kinase.

ALK is not expressed in normal lung tissue.

Crizotinib, alectinib, brigatinib, lorlatinib and ceritinib are tyrosine kinase inhibitors used for untreated ALK positive patients.

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