Profiling of apoptosis genes identifies distinct types of primary cutaneous large B cell lymphoma.
Two distinct primary cutaneous large B cell lymphomas are recognized: primary cutaneous follicle centre lymphoma (PCFCL), characterized by an excellent prognosis, and primary cutaneous large B cell lymphoma, leg-type (PCLBCL leg-type), with an unfavourable prognosis. To determine whether inhibition of the apoptosis pathways may underlie the difference in clinical outcome between PCFCL and PCLBCL leg-type, we investigated the expression of only apoptosis-related genes by microarray expression profiling. Unsupervised cluster analysis was carried out using 169 genes involved in apoptosis on a group of 21 previously untreated patients diagnosed with primary cutaneous large B cell lymphoma. Cluster analysis resulted in two separate groups which showed large overlap with the PCFCL and PCLBCL leg-type. One group was characterized by high expression levels of pro- and anti-apoptotic genes. The other group was characterized by high expression levels of apoptosis-inducing cytotoxic effector genes, possibly reflecting a cellular cytotoxic immune response. Our results suggest that the clinically favourable PCFCLs are characterized by a relatively intense cellular cytotoxic immune response and that PCLBCL leg-types are characterized by constitutive activation of the intrinsic mediated apoptosis pathway, with concomitant downstream inhibition of this apoptosis pathway. Thus, strategies neutralizing the function of apoptosis-inhibiting proteins might be effective in PCLBCL leg-type.
van Galen
J C
JC
Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands.
Hoefnagel
J J
JJ
Vermeer
M H
MH
Willemze
R
R
Dijkman
R
R
Tensen
C P
CP
de Boer
W P H
WP
Meijer
C J
CJ
Oudejans
J J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D016000:Cluster Analysis; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007866:Leg; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012535:Scalp; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D016019:Survival Analysis; D013909:Thorax