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ALK and ALCL. By Alicia Payne. What is ALK?. ALK stands for A naplastic L ymphoma K inase Transmembrane RTK. Pathways Involved with ALK. ALK and Ras-ERK Pathway. ALK and PI3K Pathway. ALK and STAT Pathway. ALK and the Ras-ERK Pathway. ALK in the Cell.

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Alk and alcl


By Alicia Payne

What is alk
What is ALK?

  • ALK stands for Anaplastic Lymphoma Kinase

  • Transmembrane RTK

Pathways involved with alk
Pathways Involved with ALK

ALK and Ras-ERK Pathway

ALK and PI3K Pathway

ALK and STAT Pathway

Alk in the cell
ALK in the Cell

  • ALK is an RTK involved in neuronal cell differentiation and regeneration, synapse formation and muscle cell migration

  • Possible ligands include Pleiotrophin (PTN) and midkine (MK)

Knockout mice
Knockout Mice

(-/-) Homozygote Mutants:

  • Viable

  • Altered behavior

  • Increased number of progenitor cells in the hippocampus

  • Reduced body weight

    Bilsland et. Al.

Alcl basics
ALCL Basics

  • ALCL = Anaplastic Large Cell Lymphoma

  • ALCL is a subset of T-cell non-Hodgkins Lymphoma

Overview of alk mutations
Overview of ALK Mutations

  • Mainly translocations  fusion proteins

  • Fusions promote dimerization which activates ALK

Npm alk fusion protein
NPM-ALK Fusion Protein

  • Oncogene

  • 70-80% of ALK-positive ALCL

  • t(2;5)(p23;q35) translocation

Alk and alcl1

  • ALK fusions increase cell migration rate and cause cytoskeletal rearrangements of lymphoid cells

  • This creates anaplastic cells or sheets in the lymph nodes


ALK-targeted therapy is promising because:

  • Can use CD30-Agonist Antibodies (in ALCL)

  • ALK is not widely expressed; few toxic effects

  • ALCL is mainly a childhood disease; search for effective long-term treatments


  • ALK

  • RTK

  • Mainly involved in nervous system develoment

  • Active in lymphoid cells where it is associated with ALCL

  • ALCL

  • Subset of T-cell NHL

  • ALK mutations cause cell migration and cytoskeletal rearrangements of lymphoid cells  anaplastic cells or sheets in the lymph nodes

  • ALK increases CD30 expression on T-cell tumor cell membranes

  • However, even though there is more CD30, it cannot activate the NFKB pathways, and cell-cycle arrest and apoptosis do not occur

  • NPM-ALK Fusion Protein

  • Main ALK mutation

  • Translocation

  • Promotes ALK dimerization and activation

  • Hyperactivation of ALK promotes cell proliferation, cell survival, migration, and cytoskeletal rearrangements  cancer


  • Chiarle, Roberto, Voena, Claudia. The anaplastic lymphoma kinase in the pathogenesis of cancer

    Nature Reviews Cancer 2008 8: 11-23

  • Kutok, Jeffery L., Aster, Jon C.Molecular Biology of Anaplastic Lymphoma Kinase-Positive Anaplastic Large-Cell LymphomaJ Clin Oncol 2002 20: 3691-3702

  • Bilsland, James G., Wheeldon, Alan. Behavioral and Neurochemical Alterations in Mice Deficient in Anaplastic Lymphoma Kinase Suggest Therapeutic Potential for Psychiatric Indications

    Neuropsychopharmacology 2008 33: 685-700