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

Histone H4 Acetylation by Immunohistochemistry. Nuclear staining for acetyl-histone H4 in Kasumi-1 cells with 5 mM of sodium butyrate.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Histone H4 Acetylation by Immunohistochemistry. Nuclear staining for acetyl-histone H4 in Kasumi-1 cells with 5 mM of sodium butyrate.

Mentions: Untreated Kasumi-1 cells exhibited no staining for acetyl-histone H4. However, upon incubation with the HDAC inhibitor sodium butyrate (2 mM or 5 mM), the Kasumi-1 cells demonstrated increased nuclear staining for acetyl-histone H4 (Figures 1, 2, 3). Western blot analysis of these cells, using the same antibody to acetyl-histone H4 as was used for immunohistochemistry, showed a similar pattern of increasing acetyl-histone H4 levels with higher concentrations of sodium butyrate (Figure 4). This demonstrates the specificity of this antibody for acetyl-histone H4.


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)

Histone H4 Acetylation by Immunohistochemistry. Nuclear staining for acetyl-histone H4 in Kasumi-1 cells with 5 mM of sodium butyrate.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Histone H4 Acetylation by Immunohistochemistry. Nuclear staining for acetyl-histone H4 in Kasumi-1 cells with 5 mM of sodium butyrate.
Mentions: Untreated Kasumi-1 cells exhibited no staining for acetyl-histone H4. However, upon incubation with the HDAC inhibitor sodium butyrate (2 mM or 5 mM), the Kasumi-1 cells demonstrated increased nuclear staining for acetyl-histone H4 (Figures 1, 2, 3). Western blot analysis of these cells, using the same antibody to acetyl-histone H4 as was used for immunohistochemistry, showed a similar pattern of increasing acetyl-histone H4 levels with higher concentrations of sodium butyrate (Figure 4). This demonstrates the specificity of this antibody for acetyl-histone H4.

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