Limits...
Histone H4 acetylation by immunohistochemistry and prognosis in newly diagnosed adult acute lymphoblastic leukemia (ALL) patients.

Advani AS, Gibson SE, Douglas E, Jin T, Zhao X, Kalaycio M, Copelan E, Sobecks R, Sekeres M, Sungren S, Hsi ED - BMC Cancer (2010)

Bottom Line: On multivariate analysis, histone acetylation was associated with a trend towards an improved OS (for all CG risk groups) (HR = 0.51, p = 0.09).This association remained statistically significant in multivariate analysis.These data provide a rationale for the design of novel regimens incorporating HDAC inhibitors in ALL.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA. advania@ccf.org

ABSTRACT

Background: Histone deacetylase (HDAC) inhibitors are a novel anti-tumor therapy. To determine whether HDAC inhibitors may be useful in the treatment of adult acute lymphoblastic leukemia (ALL), we examined the acetylation of histone H4 by immunohistochemistry in newly diagnosed ALL patients and evaluated the impact of acetylation on complete remission (CR) rate, relapse-free survival (RFS), and overall survival (OS).

Methods: Patients > or = 18 years of age and an available diagnostic bone marrow biopsy were evaluated. Cox proportional hazards analysis was used to identify univariate and multivariate correlates of CR, RFS, and OS. The variables histone H4 acetylation (positive or negative), white blood count, cytogenetic (CG) risk group (CALGB criteria), and age were used in multivariate analysis.

Results: On multivariate analysis, histone acetylation was associated with a trend towards an improved OS (for all CG risk groups) (HR = 0.51, p = 0.09). In patients without poor risk CG, there was an impressive association between the presence of histone acetylation and an improved CR rate (OR 3.43, p = 0.035), RFS (HR 0.07, p = 0.005), and OS (HR 0.24, p = 0.007). This association remained statistically significant in multivariate analysis.

Conclusions: These data provide a rationale for the design of novel regimens incorporating HDAC inhibitors in ALL.

Show MeSH

Related in: MedlinePlus

Kaplan-Meier curves of histone acetylation and relapse-free survival (RFS).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2921396&req=5

Figure 7: Kaplan-Meier curves of histone acetylation and relapse-free survival (RFS).

Mentions: Univariate and multivariate analyses for all patients, including those with poor risk cytogenetics are shown in Tables 2, 3, 4. Kaplan-Meier graphs of histone H4 acetylation and CR, relapse-free survival, and overall survival are shown in Figures 7 and 8. Histone acetylation was associated with an improved OS in all patients (HR 0.45; 95% CI 0.21-0.96, p = 0.038) (Table 4). Age at diagnosis (>35 versus ≤35), white blood count at diagnosis (>20,000/μL versus ≤20,000/μL) and cytogenetic risk group (poor versus others) were associated with a trend towards a decreased overall survival. However, this was not statistically significant (Table 4). On multivariate analysis, histone acetylation was associated with a trend towards a decreased overall survival (when evaluating all CG risk groups) (HR 0.51, 95% CI 0.23-1.13, p = 0.09). However, this was not statistically significant. Treatment (high dose cytarabine/mitoxantrone versus vincristine/prednisone based induction) was not associated with outcome.


Histone H4 acetylation by immunohistochemistry and prognosis in newly diagnosed adult acute lymphoblastic leukemia (ALL) patients.

Advani AS, Gibson SE, Douglas E, Jin T, Zhao X, Kalaycio M, Copelan E, Sobecks R, Sekeres M, Sungren S, Hsi ED - BMC Cancer (2010)

Kaplan-Meier curves of histone acetylation and relapse-free survival (RFS).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2921396&req=5

Figure 7: Kaplan-Meier curves of histone acetylation and relapse-free survival (RFS).
Mentions: Univariate and multivariate analyses for all patients, including those with poor risk cytogenetics are shown in Tables 2, 3, 4. Kaplan-Meier graphs of histone H4 acetylation and CR, relapse-free survival, and overall survival are shown in Figures 7 and 8. Histone acetylation was associated with an improved OS in all patients (HR 0.45; 95% CI 0.21-0.96, p = 0.038) (Table 4). Age at diagnosis (>35 versus ≤35), white blood count at diagnosis (>20,000/μL versus ≤20,000/μL) and cytogenetic risk group (poor versus others) were associated with a trend towards a decreased overall survival. However, this was not statistically significant (Table 4). On multivariate analysis, histone acetylation was associated with a trend towards a decreased overall survival (when evaluating all CG risk groups) (HR 0.51, 95% CI 0.23-1.13, p = 0.09). However, this was not statistically significant. Treatment (high dose cytarabine/mitoxantrone versus vincristine/prednisone based induction) was not associated with outcome.

Bottom Line: On multivariate analysis, histone acetylation was associated with a trend towards an improved OS (for all CG risk groups) (HR = 0.51, p = 0.09).This association remained statistically significant in multivariate analysis.These data provide a rationale for the design of novel regimens incorporating HDAC inhibitors in ALL.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Center, The Cleveland Clinic, Cleveland, OH, USA. advania@ccf.org

ABSTRACT

Background: Histone deacetylase (HDAC) inhibitors are a novel anti-tumor therapy. To determine whether HDAC inhibitors may be useful in the treatment of adult acute lymphoblastic leukemia (ALL), we examined the acetylation of histone H4 by immunohistochemistry in newly diagnosed ALL patients and evaluated the impact of acetylation on complete remission (CR) rate, relapse-free survival (RFS), and overall survival (OS).

Methods: Patients > or = 18 years of age and an available diagnostic bone marrow biopsy were evaluated. Cox proportional hazards analysis was used to identify univariate and multivariate correlates of CR, RFS, and OS. The variables histone H4 acetylation (positive or negative), white blood count, cytogenetic (CG) risk group (CALGB criteria), and age were used in multivariate analysis.

Results: On multivariate analysis, histone acetylation was associated with a trend towards an improved OS (for all CG risk groups) (HR = 0.51, p = 0.09). In patients without poor risk CG, there was an impressive association between the presence of histone acetylation and an improved CR rate (OR 3.43, p = 0.035), RFS (HR 0.07, p = 0.005), and OS (HR 0.24, p = 0.007). This association remained statistically significant in multivariate analysis.

Conclusions: These data provide a rationale for the design of novel regimens incorporating HDAC inhibitors in ALL.

Show MeSH
Related in: MedlinePlus