TCL1A expression delineates biological and clinical variability in B-cell lymphoma.
The assembly of a collection of gene-expression signatures of the major types of B-cell non-Hodgkin's lymphoma has identified increased T-cell leukemia/lymphoma 1A (TCL1) expression in multiple lymphoma types and cases, and has enabled the investigation of the functional and clinical importance of TCL1 expression. Specifically, Burkitt's lymphoma cases show a homogeneously strong expression of TCL1, whereas diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, nodal marginal zone lymphoma, and splenic marginal zone lymphoma display a striking variability in the intensity of TCL1 staining. This was validated in two independent series. A Gene-Set Enrichment Analysis of the genes correlated with TCL1A expression found that variation in the level of expression of TCL1A was significantly associated with some of the most important gene signatures recognizing B-cell lymphoma pathogenesis and heterogeneity, such as germinal center, B-cell receptor, NF-kappaB (and its target genes), death, MAP kinases, TNFR1, TOLL, and IL1R. Additionally, TCL1 expression was correlated with shorter time to treatment in chronic lymphocytic leukemia cases and shorter lymphoma-specific survival in mantle cell lymphoma series, thus indicating the clinical and biological significance of TCL1 expression, and suggesting TCL1A as a potential therapeutic target.
Aggarwal
Mohit
M
Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Villuendas
Raquel
R
Gomez
Gonzalo
G
Rodriguez-Pinilla
Socorro M
SM
Sanchez-Beato
Margarita
M
Alvarez
David
D
Martinez
Nerea
N
Rodriguez
Antonia
A
Castillo
Maria E
ME
Camacho
Francisca I
FI
Montes-Moreno
Santiago
S
Garcia-Marco
Jose A
JA
Kimby
Eva
E
Pisano
David G
DG
Piris
Miguel A
MA
D000368:Aged; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020522:Lymphoma, Mantle-Cell / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015203:Reproducibility of Results; D046888:Tissue Array Analysis
D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human