Expression of interleukin 15 in primary adult acute lymphoblastic leukemia.
BACKGROUND
Interleukin-15 (IL-15) has been associated with the growth, survival and biological behavior of leukemic cells and response to therapy. We determined the expression of IL-15 in lymphoblasts and evaluated its potential impact on the outcome in adult acute lymphoblastic leukemia (ALL).


METHODS
Between June 1999 and June 2006, ALL samples were collected from 87 adult patients before initiation of antineoplastic therapy. These patients were enrolled in the German Multicenter Acute Lymphoblastic Leukemia June 1999 and July 2003 study trials. The expression of IL-15 in leukemic cells was analyzed by real-time polymerase chain reaction.


RESULTS
The expression of IL-15 correlated with the immunophenotype: T-lineage ALL had a more than 4-fold higher IL-15 mRNA expression as compared with B-cell precursor (BCP)-ALL (P < .001). Patients with BCR-ABL(+)-BCP-ALL had lower IL-15 expression compared with BCR-ABL(-)-BCP-ALL (P = .041). Furthermore, higher expression of IL-15 was associated with mediastinal (P = .001) and lymph node infiltration (P = .051), but not with hepatomegaly and splenomegaly. Notably, high IL-15 expression in BCP-ALL was associated with an inferior relapse-free survival (RFS) at 5 years (0.17 +/- 0.13 vs 0.47 +/- 0.13) (P = .008), but there was no impact on overall survival (P = .249).


CONCLUSIONS
Differential expression of IL-15 in adult ALL at diagnosis was associated with clinical features and outcome, in particular, RFS. It remains to be evaluated whether IL-15 might be a relevant therapy target, or might be used for risk stratification.
Wu
Shuling
S
Department of Hematology, Oncology and Transfusion Medicine, Campus Benjamin Franklin, Charity Medical Center, Hindenburgdamm 30, 12203 Berlin, Germany. shuling.wu@charite.de
Fischer
Lars
L
Gökbuget
Nicola
N
Schwartz
Stefan
S
Burmeister
Thomas
T
Notter
Michael
M
Hoelzer
Dieter
D
Fuchs
Hendrik
H
Blau
Igor Wolfgang
IW
Hofmann
Wolf K
WK
Thiel
Eckhard
E
D000293:Adolescent; D000328:Adult; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000235:genetics*; D007621:Karyotyping; D008207:Lymphatic Metastasis; D008297:Male; D008479:Mediastinal Neoplasms / Q000556:secondary; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019409:Interleukin-15