With the object to identify key proteins related to treatment response in acute myeloid leukemia (AML), and to eventually elucidate new targets for therapy, we have investigated protein spectra from diagnostic AML samples. Surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) was used to spot proteins in the molecular weight area of 2–40 kDa. The samples were applied to two different chip surfaces (CM10 and Q10) for selective protein binding, avoiding the necessity of extensive purification and separation procedures prior to analysis. Peripheral blood samples from a total of 67 acute leukemia patients at diagnosis were analyzed. The cells were collected, frozen and stored in biobanks between 1988 and 2003. This provided a good basis for correlating detected protein peaks to a large number of clinical diagnostic and therapeutic variables and outcomes. Among the patients, aged 18 to 86 yrs, response to induction therapy was observed with complete remission (CR) durations ranging between 12 and 3701 days. The duration of first CR was used as a dichotomic variable in order to compare protein spectra from groups of patients with “good” and “bad” response, respectively, to chemotherapy. A peak detection and annotation software was developed in-house1,2 and employed. The software will be presented and a comparison to commercially available MS-spectral analysis methods will be provided. Initial results from MS profiling of the two response groups showed 18 significantly (p>0.01) differently expressed peaks on anion exchange chips and 22 peaks on cation exchange surfaces. Ongoing work is focused on further development of the RS peak detection method, including the influence of normalisation and filtering of the SELDI data and supervised linear and non-linear modelling. In addition, identification of selected peaks and their relation to various clinical variables is in progress.

Topics:
anions, biobanks, biological markers, cations, chemotherapy regimen, complete remission, ionization, lasers, leukemia, acute, leukemia, myelocytic, acute

Disclosure: No relevant conflicts of interest to declare.

1.
Chuen Seng Tan et al: Finding regions of significance in SELDI measurements for identifying protein biomarkers, Bioinformatics, March 27 (
2006
).
2.
The R-package ProSpect that implements RS is freely available for academic use, available at http://www.meb.ki.se/~yudpaw.

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2006, The American Society of Hematology
2006
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