Anaplastic lymphoma kinase: Difference between revisions

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'''Anaplastic lymphoma kinase''' ('''ALK''') is a [[tyrosine kinase]] receptor that is encoded by the '''ALK''' gene in humans. It plays a crucial role in the development of the brain and exerts its effects on specific neurons in the nervous system. ALK is involved in various cellular processes, including cell growth, differentiation, and survival.
{{Infobox enzyme
| Name = Anaplastic lymphoma kinase
| EC_number = 2.7.10.1
| CAS_number = 138982-67-9
| IUBMB_EC_number = 2/7/10/1
| GO_code = 0046875
}}


==Structure and Function==
'''Anaplastic lymphoma kinase''' ('''ALK''') is an enzyme that in humans is encoded by the ''ALK'' gene. ALK is a receptor [[tyrosine kinase]] that is important in the development of the brain. Abnormal expression of ALK is implicated in several diseases, including certain types of [[cancer]].
ALK is a member of the [[insulin receptor]] superfamily and is characterized by an extracellular domain, a single transmembrane domain, and an intracellular tyrosine kinase domain. The receptor is activated through ligand binding, which leads to autophosphorylation and subsequent activation of downstream signaling pathways such as the [[PI3K/AKT pathway]], [[MAPK/ERK pathway]], and [[JAK/STAT pathway]].


==Role in Cancer==
== Function ==
Mutations and rearrangements in the ALK gene are implicated in several types of [[cancer]]. The most notable of these is [[anaplastic large-cell lymphoma]] (ALCL), a type of [[non-Hodgkin lymphoma]]. ALK rearrangements are also found in a subset of [[non-small cell lung cancer]] (NSCLC) and [[neuroblastoma]].
ALK plays a crucial role in the development and function of the nervous system. It is a receptor tyrosine kinase in the [[insulin receptor]] superfamily, which includes the [[leukocyte tyrosine kinase]] (LTK) gene family. ALK helps in the brain development by influencing the growth and differentiation of [[neuron]]s.


===Anaplastic Large-Cell Lymphoma===
== Clinical significance ==
In ALCL, the ALK gene is often fused with the [[nucleophosmin]] (NPM) gene, resulting in the NPM-ALK fusion protein. This fusion protein is constitutively active, leading to uncontrolled cell proliferation and survival.
### Cancer ###
ALK is best known for its role in certain types of cancers. The most notable association is with [[anaplastic large cell lymphoma]] (ALCL), where chromosomal translocations involving the ALK gene are often observed. These translocations create fusion genes that are oncogenic, leading to cancerous cell growth.


===Non-Small Cell Lung Cancer===
### Lung Cancer ###
In NSCLC, ALK rearrangements typically involve the [[echinoderm microtubule-associated protein-like 4]] (EML4) gene, creating the EML4-ALK fusion protein. This fusion protein is also constitutively active and drives oncogenesis.
In [[non-small cell lung cancer]] (NSCLC), ALK rearrangements account for about 3-7% of cases. The identification of ALK rearrangements in NSCLC has led to the development of ALK inhibitors, such as crizotinib, which have shown significant efficacy in treating ALK-positive NSCLC.


===Neuroblastoma===
### Neuroblastoma ###
ALK mutations are found in both familial and sporadic cases of neuroblastoma, a cancer that arises from [[neural crest]] cells. These mutations often result in constitutive activation of the ALK receptor, promoting tumorigenesis.
ALK mutations are also found in [[neuroblastoma]], a common cancer in children. These mutations are typically activating mutations, leading to increased kinase activity and oncogenic signaling.


==Diagnosis and Treatment==
== Diagnosis and Treatment ==
The detection of ALK rearrangements and mutations is crucial for the diagnosis and treatment of ALK-positive cancers. Techniques such as [[fluorescence in situ hybridization]] (FISH), [[immunohistochemistry]] (IHC), and [[next-generation sequencing]] (NGS) are commonly used for this purpose.
The detection of ALK gene rearrangements in cancers is typically performed using fluorescence in situ hybridization (FISH) or next-generation sequencing. The presence of ALK rearrangements can influence the treatment strategy, with ALK inhibitors being a preferred treatment option for ALK-positive tumors.


===Targeted Therapy===
== See also ==
Several ALK inhibitors have been developed for the treatment of ALK-positive cancers. These include [[crizotinib]], [[ceritinib]], [[alectinib]], and [[lorlatinib]]. These drugs specifically target the ALK tyrosine kinase domain, inhibiting its activity and thereby reducing tumor growth and proliferation.
* [[Tyrosine kinase inhibitor]]
 
* [[Crizotinib]]
==Research and Future Directions==
* [[Cancer therapy]]
Ongoing research aims to better understand the mechanisms of ALK activation and resistance to ALK inhibitors. Newer generations of ALK inhibitors and combination therapies are being explored to improve outcomes for patients with ALK-positive cancers.
 
==See Also==
* [[Tyrosine kinase]]
* [[Non-Hodgkin lymphoma]]
* [[Non-small cell lung cancer]]
* [[Neuroblastoma]]
* [[Targeted therapy]]
 
==References==
{{Reflist}}
 
==External Links==
{{Wikidata|Q210000}}


[[Category:Tyrosine kinases]]
[[Category:Oncology]]
[[Category:Oncology]]
[[Category:Tyrosine kinases]]
[[Category:Genes on human chromosome 2]]
[[Category:Genes on human chromosome 2]]
[[Category:Receptor tyrosine kinases]]
[[Category:Signal transduction]]


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Latest revision as of 16:01, 13 August 2024

Anaplastic lymphoma kinase






Anaplastic lymphoma kinase (ALK) is an enzyme that in humans is encoded by the ALK gene. ALK is a receptor tyrosine kinase that is important in the development of the brain. Abnormal expression of ALK is implicated in several diseases, including certain types of cancer.

Function[edit]

ALK plays a crucial role in the development and function of the nervous system. It is a receptor tyrosine kinase in the insulin receptor superfamily, which includes the leukocyte tyrosine kinase (LTK) gene family. ALK helps in the brain development by influencing the growth and differentiation of neurons.

Clinical significance[edit]

      1. Cancer ###

ALK is best known for its role in certain types of cancers. The most notable association is with anaplastic large cell lymphoma (ALCL), where chromosomal translocations involving the ALK gene are often observed. These translocations create fusion genes that are oncogenic, leading to cancerous cell growth.

      1. Lung Cancer ###

In non-small cell lung cancer (NSCLC), ALK rearrangements account for about 3-7% of cases. The identification of ALK rearrangements in NSCLC has led to the development of ALK inhibitors, such as crizotinib, which have shown significant efficacy in treating ALK-positive NSCLC.

      1. Neuroblastoma ###

ALK mutations are also found in neuroblastoma, a common cancer in children. These mutations are typically activating mutations, leading to increased kinase activity and oncogenic signaling.

Diagnosis and Treatment[edit]

The detection of ALK gene rearrangements in cancers is typically performed using fluorescence in situ hybridization (FISH) or next-generation sequencing. The presence of ALK rearrangements can influence the treatment strategy, with ALK inhibitors being a preferred treatment option for ALK-positive tumors.

See also[edit]


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