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Overexpression of X-linked inhibitor of apoptosis protein (XIAP) is an independent unfavorable prognostic factor in childhood de novo acute myeloid leukemia.

Sung KW, Choi J, Hwang YK, Lee SJ, Kim HJ, Kim JY, Cho EJ, Yoo KH, Koo HH - J. Korean Med. Sci. (2009)

Bottom Line: The overexpression of X-linked inhibitor of apoptosis protein (XIAP), a member of IAP family protein, is intuitively expected to be associated with unfavorable clinical features in malignancies; however, there have been only a very limited number of studies reporting the clinical relevance of XIAP expression.As a result, the XIAP expression was found to be higher in patients with extramedullary disease than in those without (P=0.014).Multivariate analyses revealed that XIAP overexpression was an independent unfavorable prognostic factor for relapse-free survival (hazard ratio, 6.16; 95% confidence interval, 1.48-25.74; P=0.013).

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT
The overexpression of X-linked inhibitor of apoptosis protein (XIAP), a member of IAP family protein, is intuitively expected to be associated with unfavorable clinical features in malignancies; however, there have been only a very limited number of studies reporting the clinical relevance of XIAP expression. This study was performed to investigate the prognostic relevance of XIAP expression in childhood acute myeloid leukemia (AML). In 53 children with de novo AML, the level of XIAP expression was determined by using quantitative reverse transcriptase-polymerase chain reaction and was analyzed with respect to the clinical characteristics at diagnosis and treatment outcomes. As a result, the XIAP expression was found to be higher in patients with extramedullary disease than in those without (P=0.014). In addition, XIAP overexpression (>or=median expression) was associated with an unfavorable day 7 response to induction chemotherapy and also associated with a worse 3-yr relapsefree survival rate (52.7+/-20.9% vs. 85.9+/-14.8%, P=0.014). Multivariate analyses revealed that XIAP overexpression was an independent unfavorable prognostic factor for relapse-free survival (hazard ratio, 6.16; 95% confidence interval, 1.48-25.74; P=0.013). Collectively, XIAP overexpression may be used as an unfavorable prognostic marker in childhood AML.

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XIAP overexpression: association with a worse early response to induction chemotherapy. The level of XIAP expression was higher in patients with an unfavorable day 7 response (defined as leukemic blasts > 5% on the bone marrow aspirate on day 7, the presence of a leukemic cell cluster[s] on the bone marrow biopsy section on day 7 or persistence of circulating leukemic blasts in the peripheral blood on day 7) than in those with a favorable day 7 response (absence of any of the above findings indicating an unfavorable response) (A). The proportion of patients with an unfavorable day 7 response was higher in patients with high XIAP expression (≥median) than in patients with low XIAP expression (<median) (B). In the cytotoxicity assay, the percentage of surviving leukemic blasts after 24 hr culture with etoposide was higher in patients with high XIAP expression (upper one-third, n=2) than in those with low XIAP expression (lower one-third, n=2) (C).
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Figure 2: XIAP overexpression: association with a worse early response to induction chemotherapy. The level of XIAP expression was higher in patients with an unfavorable day 7 response (defined as leukemic blasts > 5% on the bone marrow aspirate on day 7, the presence of a leukemic cell cluster[s] on the bone marrow biopsy section on day 7 or persistence of circulating leukemic blasts in the peripheral blood on day 7) than in those with a favorable day 7 response (absence of any of the above findings indicating an unfavorable response) (A). The proportion of patients with an unfavorable day 7 response was higher in patients with high XIAP expression (≥median) than in patients with low XIAP expression (<median) (B). In the cytotoxicity assay, the percentage of surviving leukemic blasts after 24 hr culture with etoposide was higher in patients with high XIAP expression (upper one-third, n=2) than in those with low XIAP expression (lower one-third, n=2) (C).

Mentions: The levels of XIAP expression with respect to responses to chemotherapy are also presented in Table 2. XIAP overexpression (≥median) was associated with a worse early response to induction chemotherapy. The level of XIAP expression was higher in patients with an unfavorable day 7 response (defined as leukemic blasts >5% on the bone marrow aspirate on day 7, the presence of a leukemic cell cluster(s) on the bone marrow biopsy section on day 7 or persistence of circulating leukemic blasts in the peripheral blood on day 7) than in those with a favorable day 7 response (absence of any of the three aforementioned findings indicating an unfavorable response) (P=0.006; Fig. 2A). Similarly, the proportion of patients with an unfavorable day 7 response was higher in patients with XIAP overexpression (≥median) than in those without (40.9% vs. 15.0%, P=0.063; Fig. 2B). In the cytotoxicity assay, the percentage of surviving leukemic blasts after 24 hr culture with etoposide was higher in patients with high XIAP expression (upper one-third) than in patients with low XIAP expression (lower one-third) (P=0.054; Fig. 2C). The level of XIAP expression was also higher in the patients who did not achieve CR after primary induction chemotherapy than in those who did; however, the difference was not significant. Similarly, the induction failure rate with primary induction chemotherapy regimen due to poor response was higher in patients with XIAP overexpression (6 out of 27) than in those without (2 out of 26), albeit without a statistical significance (P=0.138).


Overexpression of X-linked inhibitor of apoptosis protein (XIAP) is an independent unfavorable prognostic factor in childhood de novo acute myeloid leukemia.

Sung KW, Choi J, Hwang YK, Lee SJ, Kim HJ, Kim JY, Cho EJ, Yoo KH, Koo HH - J. Korean Med. Sci. (2009)

XIAP overexpression: association with a worse early response to induction chemotherapy. The level of XIAP expression was higher in patients with an unfavorable day 7 response (defined as leukemic blasts > 5% on the bone marrow aspirate on day 7, the presence of a leukemic cell cluster[s] on the bone marrow biopsy section on day 7 or persistence of circulating leukemic blasts in the peripheral blood on day 7) than in those with a favorable day 7 response (absence of any of the above findings indicating an unfavorable response) (A). The proportion of patients with an unfavorable day 7 response was higher in patients with high XIAP expression (≥median) than in patients with low XIAP expression (<median) (B). In the cytotoxicity assay, the percentage of surviving leukemic blasts after 24 hr culture with etoposide was higher in patients with high XIAP expression (upper one-third, n=2) than in those with low XIAP expression (lower one-third, n=2) (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 2: XIAP overexpression: association with a worse early response to induction chemotherapy. The level of XIAP expression was higher in patients with an unfavorable day 7 response (defined as leukemic blasts > 5% on the bone marrow aspirate on day 7, the presence of a leukemic cell cluster[s] on the bone marrow biopsy section on day 7 or persistence of circulating leukemic blasts in the peripheral blood on day 7) than in those with a favorable day 7 response (absence of any of the above findings indicating an unfavorable response) (A). The proportion of patients with an unfavorable day 7 response was higher in patients with high XIAP expression (≥median) than in patients with low XIAP expression (<median) (B). In the cytotoxicity assay, the percentage of surviving leukemic blasts after 24 hr culture with etoposide was higher in patients with high XIAP expression (upper one-third, n=2) than in those with low XIAP expression (lower one-third, n=2) (C).
Mentions: The levels of XIAP expression with respect to responses to chemotherapy are also presented in Table 2. XIAP overexpression (≥median) was associated with a worse early response to induction chemotherapy. The level of XIAP expression was higher in patients with an unfavorable day 7 response (defined as leukemic blasts >5% on the bone marrow aspirate on day 7, the presence of a leukemic cell cluster(s) on the bone marrow biopsy section on day 7 or persistence of circulating leukemic blasts in the peripheral blood on day 7) than in those with a favorable day 7 response (absence of any of the three aforementioned findings indicating an unfavorable response) (P=0.006; Fig. 2A). Similarly, the proportion of patients with an unfavorable day 7 response was higher in patients with XIAP overexpression (≥median) than in those without (40.9% vs. 15.0%, P=0.063; Fig. 2B). In the cytotoxicity assay, the percentage of surviving leukemic blasts after 24 hr culture with etoposide was higher in patients with high XIAP expression (upper one-third) than in patients with low XIAP expression (lower one-third) (P=0.054; Fig. 2C). The level of XIAP expression was also higher in the patients who did not achieve CR after primary induction chemotherapy than in those who did; however, the difference was not significant. Similarly, the induction failure rate with primary induction chemotherapy regimen due to poor response was higher in patients with XIAP overexpression (6 out of 27) than in those without (2 out of 26), albeit without a statistical significance (P=0.138).

Bottom Line: The overexpression of X-linked inhibitor of apoptosis protein (XIAP), a member of IAP family protein, is intuitively expected to be associated with unfavorable clinical features in malignancies; however, there have been only a very limited number of studies reporting the clinical relevance of XIAP expression.As a result, the XIAP expression was found to be higher in patients with extramedullary disease than in those without (P=0.014).Multivariate analyses revealed that XIAP overexpression was an independent unfavorable prognostic factor for relapse-free survival (hazard ratio, 6.16; 95% confidence interval, 1.48-25.74; P=0.013).

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT
The overexpression of X-linked inhibitor of apoptosis protein (XIAP), a member of IAP family protein, is intuitively expected to be associated with unfavorable clinical features in malignancies; however, there have been only a very limited number of studies reporting the clinical relevance of XIAP expression. This study was performed to investigate the prognostic relevance of XIAP expression in childhood acute myeloid leukemia (AML). In 53 children with de novo AML, the level of XIAP expression was determined by using quantitative reverse transcriptase-polymerase chain reaction and was analyzed with respect to the clinical characteristics at diagnosis and treatment outcomes. As a result, the XIAP expression was found to be higher in patients with extramedullary disease than in those without (P=0.014). In addition, XIAP overexpression (>or=median expression) was associated with an unfavorable day 7 response to induction chemotherapy and also associated with a worse 3-yr relapsefree survival rate (52.7+/-20.9% vs. 85.9+/-14.8%, P=0.014). Multivariate analyses revealed that XIAP overexpression was an independent unfavorable prognostic factor for relapse-free survival (hazard ratio, 6.16; 95% confidence interval, 1.48-25.74; P=0.013). Collectively, XIAP overexpression may be used as an unfavorable prognostic marker in childhood AML.

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Related in: MedlinePlus