Expression of interleukin-10 splicing variants is a positive prognostic feature in relapsed childhood acute lymphoblastic leukemia

Biologic features of hematologic malignancies have prognostic implications and are essential elements in the design of current therapeutic trials. This study aimed to determine the expression of a splicing-derived variant of interleukin (IL) -10 in leukemic cells and its clinical relevance in childr...

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Veröffentlicht in:Journal of clinical oncology Jg. 23; H. 13; S. 3038
Hauptverfasser: Wu, Shuling, Gessner, Reinhard, Taube, Tillmann, von Stackelberg, Arend, Henze, Günter, Seeger, Karl
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.05.2005
Schlagworte:
Adolescent
Alternative Splicing
Child
Child, Preschool
Female
Gene Expression Profiling
Genetic Variation
Humans
Immunoblotting
Infant
Interleukin-10 - genetics
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Prognosis
Recurrence
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Treatment Outcome
ISSN:0732-183X
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Zusammenfassung:Biologic features of hematologic malignancies have prognostic implications and are essential elements in the design of current therapeutic trials. This study aimed to determine the expression of a splicing-derived variant of interleukin (IL) -10 in leukemic cells and its clinical relevance in children with acute lymphoblastic leukemia (ALL) at first relapse. Between January 1997 and December 2001, bone marrow (BM) samples were collected from 98 children with first relapse of ALL at diagnosis. These patients were enrolled in the relapse trial ALL-REZ BFM (ALL-Relapse Berlin-Frankfurt-Munster) 95 and 96. The detection of IL-10 isoforms in leukemic cells of BM samples were performed by conventional reverse transcriptase polymerase chain reaction and by immunoblotting. IL-10 was detected in 93.9% BM samples. In addition to expressing full-length IL-10, a new splicing-derived IL-10 variant (termed IL-10delta3) that lacked the entire exon 3 was identified in leukemic cells. The IL-10delta3 variant was found in 80.4% of BM samples. Most importantly, expression of IL-10delta3 was associated with a significantly better response to chemotherapy (P = .001) and probability of event-free survival (P = .01) at 5 years. These results indicate that splicing-derived IL-10 isoforms may modulate IL-10-mediated biologic effects and therapeutic efficacy in lymphatic disease, and expression of IL-10delta3 is a positive prognostic feature in relapsed childhood ALL.
Bibliographie:ObjectType-Article-1
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ISSN:0732-183X
DOI:10.1200/JCO.2005.00.885