High expression of several tyrosine kinases and activation of the PI3K/AKT pathway in mediastinal large B cell lymphoma reveals further similarities to Hodgkin lymphoma.
Mediastinal large B-cell (MBL) and classical Hodgkin lymphoma (HL) have several pathogenic mechanisms in common. As we recently observed aberrant tyrosine kinase (TK) activities in HL, we now analysed also MBL for such activities. Indeed, MBL and HL were the only B-cell lymphomas where elevated cellular phospho-tyrosine contents were typical features. Three TKs, JAK2, RON and TIE1, not expressed in normal B cells, were each expressed in about 30% of MBL cases, and 75% of cases expressed at least one of the TKs. Among the intracellular pathways frequently triggered by TKs, the PI3K/AKT pathway was activated in about 40% of MBLs and essential for survival of MBL cell lines, whereas the RAF/mitogen-activated protein kinase pathway seemed to be inhibited. No activating mutations were detected in the three TKs in MBL cell lines and primary cases. RON and TIE1 were each also expressed in about 35% and JAK2 in about 53% of HL cases. JAK2 genomic gains are frequent in MBL and HL but we observed no strict correlation of JAK2 genomic status with JAK2 protein expression. In conclusion, aberrant TK activities are a further shared pathogenic mechanism of MBL and HL and may be interesting targets for therapeutic intervention.
Renné
C
C
Senckenberg Institute for Pathology, University of Frankfurt, Frankfurt, Germany.
Willenbrock
K
K
Martin-Subero
J I
JI
Hinsch
N
N
Döring
C
C
Tiacci
E
E
Klapper
W
W
Möller
P
P
Küppers
R
R
Hansmann
M-L
ML
Siebert
R
R
Bräuninger
A
A
D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051058:Oncogene Protein v-akt