During the last year the expression of anaplastic lymphoma kinase clarified presentation and provided clues toward the outcome of anaplastic large cell lymphoma; the breakpoints of t(2;5) were mapped; constitutive activation of anaplastic lymphoma kinase by a chromosomal inversion was described; transformation was shown to be independent of nuclear localization of anaplastic lymphoma kinase; and phospholipase C-gamma was identified as a molecular target for the kinase activity of anaplastic lymphoma kinase.
Systemic anaplastic large-cell lymphoma (ALCL) is a childhood T cell neoplasm defined by the presence or absence of translocations that lead to the ectopic expression of anaplastic lymphoma kinase (ALK), with nucleophosmin-ALK (NPM-ALK) fusions being the most common.
It induces JAK3/STAT3 signaling, a biologically important cellular pathway activated in most cases of anaplastic lymphoma kinase (ALK)-expressing anaplastic large cell lymphoma (ALK(+)ALCL).
Accumulating evidence indicates that expression of anaplastic lymphoma kinase (ALK), typically due to t(2;5) translocation that creates an NPM-ALK fusion gene, defines a distinct type of T/null-cell lymphoma (TCL) within a vastly heterogeneous group of anaplastic large cell lymphomas.
Anaplastic Lymphoma Kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in a variety of tumor types, most notably in Anaplastic Large Cell Lymphoma (ALCL) where a chromosomal translocation generates the oncogenic fusion protein, Nucleophosmin-ALK (NPM-ALK).
The majority of these neoplasms in the United States are anaplastic large cell lymphomas (ALCL) characterized by CD30 and anaplastic lymphoma kinase-1 expression.
Systemic anaplastic large cell lymphoma is composed of two disease groups based on the presence or absence of anaplastic lymphoma kinase overexpression.
These findings indicate that TFG can provide an alternative to NPM as a fusion partner responsible for activation of the ALK and the pathogenesis of ALCL.
We analyzed SHP1 tyrosine phosphatase expression and activity in 3 ALK-positive ALCL cell lines (Karpas 299, Cost, and SU-DHL1) and in lymph node biopsies (n = 40).
In order to investigate the expression profiles of ALCLs carrying the NPM-ALK and TPM3-ALK fusions, we carried out cDNA microarray analysis of two ALCL tissue samples, one expressing the NPM-ALK fusion protein and the other the TPM3-ALK fusion protein.
Anaplastic large cell lymphomas (ALCLs) are rare CD30+ peripheral T-cell lymphomas (PTCLs) classified according to the expression of the anaplastic lymphoma kinase (ALK+) protein or not (ALK-).
In the present study, we used novel antibodies to compare ALK protein expression in genetically defined lung cancers and anaplastic large cell lymphomas.
Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive (ALK+ ALCL) is an aggressive CD30-positive T-cell lymphoma that exhibits a chromosomal translocation involving the ALK gene and the expression of ALK protein.
Furthermore, full length receptor expression is absent in cell lines of the hematopoietic system with the exception of t(2;5)-associated anaplastic large cell lymphomas lines (ALCL), which are known to express chimeric NPM-ALK mRNA.
Neoplastic cells in the majority of ALCL expressed cyclin D1 mRNA (29/41 [70.7%]), in association with the presence of ALK translocations (p=0.024) and systemic, rather than cutaneous disease (p=0.021).
We further evaluated the relationship between TIMP1 expression and STAT3 activation in 43 ALCL tumors (19 ALK(+) and 24 ALK(-)) using immunohistochemistry and a tissue microarray.
Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes.