High Interleukin-15 Expression Characterizes Childhood Acute Lymphoblastic Leukemia With Involvement of the CNS

Cario, Gunnar; Izraeli, Shai; Teichert, Anja; Rhein, Peter; Skokowa, Julia; Möricke, Anja; Zimmermann, Martin; Schrauder, André; Karawajew, Leonid; Ludwig, Wolf Dieter; Welte, Karl; Schünemann, Holger J.; Schlegelberger, Brigitte; Schrappe, Martin; Stanulla, Martin

doi:10.1200/jco.2007.11.8166

Cited by 89 publications

(73 citation statements)

References 34 publications

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“…It has been shown that high expression of IL-15 correlates with CNS disease in pediatric ALL. 10 However, we found that IL-15 does not correlate in our series of adult patients with BCR-ABL negative ALL. These results may be in conjunction with multifunctional signals mediated by IL-15 and its unusual pattern of expression and secretion.…”

Section: Discussioncontrasting

confidence: 60%

“…8,9 Recently, the powerful antiapoptotic properties of IL-15 have been suggested to confer a selective growth advantage to neoplastic cells promoting tumor cell growth, expansion, and organ infiltration of malignancies. 3,[7][8][9][10] Concerning the clinical relevance of IL-15 in hematopoietic malignancies, elevated IL-15 levels have been shown to affect the initial response to therapy and were associated with malignant transformation, including organ infiltration and disease progression, such as relapse. 3,[10][11][12][13] In adult ALL, clinical studies have defined immunophenotype and molecular genetic markers, as well as the duration of first remission, as the most significant independent prognostic determinants.…”

mentioning

confidence: 99%

“…3,[7][8][9][10] Concerning the clinical relevance of IL-15 in hematopoietic malignancies, elevated IL-15 levels have been shown to affect the initial response to therapy and were associated with malignant transformation, including organ infiltration and disease progression, such as relapse. 3,[10][11][12][13] In adult ALL, clinical studies have defined immunophenotype and molecular genetic markers, as well as the duration of first remission, as the most significant independent prognostic determinants. 1,2,14 However, the improved understanding of the biology of adult ALL and identification of specific risk factors remains an important issue.…”

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confidence: 99%

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Expression of interleukin 15 in primary adult acute lymphoblastic leukemia

Fischer²,

Gökbuget

et al. 2009

Cancer

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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. Cancer 2010. © 2010 American Cancer Society.

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Section: Discussioncontrasting

confidence: 60%

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confidence: 99%

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confidence: 99%

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Expression of interleukin 15 in primary adult acute lymphoblastic leukemia

Fischer²,

Gökbuget

et al. 2009

Cancer

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“…A high expression of IL-15 correlates with CNS disease in childhood ALL 55,56 and neurocognitive impairment. 57 Moreover, several IL-15 single nucleotide polymorphisms (SNPs) have been associated with minimal residual disease; 58 five SNPs (rs10519612, rs10519613, rs35964658, rs17007695, and rs17015014) located in the IL-15 locus were associated with childhood ALL treatment response.…”

Section: Allmentioning

confidence: 99%

IL-15 as a potential target in leukemia

Xiong¹,

Bensoussan²,

Decot³

2015

BLCTT

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Leukemia, one of the most aggressive hematopoietic malignancies, is characterized by excessive proliferation, survival, and impaired differentiation of hematopoietic stem cells. Interleukin 15, a proinflammatory cytokine, induces proliferation and promotes cell survival of human T and B lymphocytes, as well as natural killer cells. However, it may also play a detrimental role in the onset of leukemia. This review provided an overview of the aberrant expression of Interleukin 15 and its role in the development and progression of this hematological malignancy. Also, we critically explored the potential therapeutic opportunities involved in targeting the disruption of interleukin-15 signaling as well as in interleukin-15-mediated enhancement of antitumor immunity.

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“…These facts suggest that IL-15 may act as a cancer development stimulator in leukemia and lymphomas originating from B cell, T cell and NK cell. Observations such as activated of expression of IL-15 and IL-15R alfa by viral Tax protein in HTLV 1 associated T cell leukemia/lymphoma as well as association of IL-15 expression with mediastinal lymphadenopathy in acute lymphoblastic leukemia (ALL) and poor prognosis and inferior 5 year survival in B cell type ALL and higher risk of CNS relapse in pediatric ALL further supports that IL-15 may act as a cancer development cytokine in hematological malignancies originating from lymphoid cell lines [146,147]. However, observations in solid tumor and cancer cell lines did not show any direct effect of IL-15.…”

Section: Other Interleukinsmentioning

confidence: 82%