Apoptosis stimulating protein of p53 (ASPP2) expression differs in diffuse large B-cel and follicular center lymphoma: Correlation with clinical outcome

Izidore S. Lossos, Yasodha Natkunam, Ronald Levy, Charles Lopez

    Research output: Contribution to journalArticle

    47 Citations (Scopus)

    Abstract

    ASPP2 interacts with the tumor suppressor protein p53, promotes damage-induced apoptosis, and can specifically stimulate p53 apoptotic function. Thus, ASPP2 may function as a tumor suppressor and/or play a role in the cellular response to cytotoxic injury. To explore the role of ASPP2 in human cancer, we determined ASPP2 expression in two lymphoma subtypes with differing clinical outcomes: diffuse large B-cell lymphoma (DLBCL) and follicular center lymphoma (FCL). A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed to detect ASPP2 mRNA. Sixty-one DLBCL and twenty-three FCL cases were analyzed and normalized ASPP2 levels were expressed relative to an mRNA standard. We found that ASPP2 mean expression strongly correlated with lymphoma subtype: DLBCL = 11.74 and FCL = 4.99 (p = 0.029, unpaired 2-tailed t-test). Importantly, ASPP2 expression was variable in DLBCL but not FCL (DLBCL-range, 0.04-94.6; FCL-range, 1.2-15.0). In these DLBCL cases, serum lactate dehydrogenase (LDH) was an independent predictor of survival with median survival in the high LDH group of 24 months and median survival not achieved in the normal-low LDH group (p = 0.014, Log-Rank Test). Mean ASPP2 levels trended toward an inverse correlation with LDH levels: High LDH, ASPP2 = 6.2; Normal-low LDH, ASPP2 = 18.2 (p = 0.074, unpaired 2-tailed t-test). In the DLBCL cases with ASPP2 levels > 7.8, only 10% (1/10) had a high LDH, in contrast to cases with ASPP2 levels <7.8 in which 59% (26/44) had a high LDH (p = 0.011, Fisher Exact Test). Thus, low ASPP2 mRNA levels may correlate with poor clinical outcome in lymphoma which is consistent with the hypothesis that ASPP2 may play a role in tumor formation and/or sensitivity to cytotoxic agents. Larger studies as well as analysis of different tumor types are warranted.

    Original languageEnglish (US)
    Pages (from-to)2309-2317
    Number of pages9
    JournalLeukemia and Lymphoma
    Volume43
    Issue number12
    DOIs
    StatePublished - Dec 1 2002

    Fingerprint

    Follicular Lymphoma
    Lymphoma, Large B-Cell, Diffuse
    L-Lactate Dehydrogenase
    Apoptosis
    Proteins
    Messenger RNA
    Survival
    Lymphoma
    Neoplasms
    Tumor Suppressor Protein p53
    Cytotoxins
    B-Cell Lymphoma
    Reverse Transcription
    Polymerase Chain Reaction
    Wounds and Injuries
    Serum

    ASJC Scopus subject areas

    • Cancer Research
    • Hematology
    • Oncology

    Cite this

    Apoptosis stimulating protein of p53 (ASPP2) expression differs in diffuse large B-cel and follicular center lymphoma : Correlation with clinical outcome. / Lossos, Izidore S.; Natkunam, Yasodha; Levy, Ronald; Lopez, Charles.

    In: Leukemia and Lymphoma, Vol. 43, No. 12, 01.12.2002, p. 2309-2317.

    Research output: Contribution to journalArticle

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