Abstract A58: Super SILAC proteomics for childhood blood cancers
Authors: Haskins William E. 
Published: December 2010

The increased incidence (1,2) and poorer outcome (3-5) of minority children with childhood acute lymphoblastic leukemia (cALL) is a well-known and significant cancer health disparity. In 2000, Pollock et al showed that the 5-year relapse-free survival (RFS) rates were 81.9 ± 0.6%, 68.6 ± 2.1 %, and 74.9 ± 2.0% for non-Hispanic/Latino white (W), African-American (AA), and Hispanic/Latino (H/L) children (3). Adjusting for age, leukocyte count, sex, era of treatment, and leukemia blast cell ploidy, AA children had a 42% excess mortality rate and H/L children had a 33% excess mortality rate compared to W children. More recent studies are in excellent agreement with this work (4,5). For example, Batia et al showed that 5-year RFS rates were: Asian, 75.1 ± 3.5%; W, 72.8 ± 0.6%; H/L, 65.9 ± 1.5%; and AA, 61.5 ± 2.2%; among patients with high-risk features (age &lt; 1 or &gt; 10; leukocyte count &gt; 50,000) (5). Adjusting for the same factors as above, H/L children had the worst outcome with a 40% excess mortality rate. The U.S. Census Bureau predicts that minority children will comprise 62% (vs. 44% in 2008) of the U.S. population by 2050, where 39% are projected to be H/L (vs. 22% in 2008) and 38% are projected to be W (vs. 56% in 2008). However, novel protein therapeutic targets and biomarkers, that reflect real-world socioeconomic and environmental factors (e.g., ethnicity, age, sex, nutrition, healthcare and exposure to chemicals, infectious diseases or radiation), are still needed to improve outcome.

In 2010, an astonishing 4336 of 5175 identified protein isoforms were quantified in breast cancer specimens by “super” stable isotopic labeling of amino acids in culture (SILAC) proteomics (7, 8). The main advantage of SILAC over other isotopic labeling techniques is that labeling is done at the protein level to enable the addition of internal standards prior to downstream and often irreproducible separations and digestions. Super SILAC additionally enables the incorporation of hundreds of thousands of isotopically labeled peptides in appropriate amounts, from multiple cell lines, to serve as internal standards. This maximizes the number of protein isoforms that can be accurately and precisely quantified with an error of a few percent and minimizes the cost because there is no need to synthesize large numbers of isotopically-labeled peptides.

We hypothesize that novel protein therapeutic targets and biomarkers for childhood blood cancers will be discovered by developing and exploiting the power of super SILAC proteomics. Preliminary results will be presented that begin to test this hypothesis.

References:

1. Wilkinson JD et al. Revista Panamericana De Salud Publica. Pan American Journal of Public Health. 18,5 (Jul, 2005).

2. Howe H et al. Cancer. 107,1711 (Oct, 2006).

3. Pollock BH et al. J Clin Oncol. 18,813 (Feb, 2000).

4. Kang H et al. Blood. (Oct 30,2009).

5. Bhatia S et al. Blood. 100,1957 (Sep 15,2002).

6. U.S. Census Bureau (http://www.census.gov/population/www/projections/), 2008.

7. Geiger T et al. Nat Methods. 7,383 (May, 2010).

8. Neubert TA etal. Nat Methods. 7,361 (May, 2010).

Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A58.