Changes in donor numbers and population-specific MP induced by optimal recruitment of n = 5,000,000 donors.

<p>Chinese donors and patients were not included in the analysis.</p

MP by registry size and composition for a combined patient population from a registry including Spanish and German donors.

<p>The green line indicates the optimal path of donor recruitment.</p

Matching probabilities for various patient populations (green: Spanish, red: German, blue: combined) by the share of Spanish donors among <i>n</i> = 500,000 new donors.

<p>Matching probabilities for various patient populations (green: Spanish, red: German, blue: combined) by the share of Spanish donors among <i>n</i> = 500,000 new donors.</p

Overview on populations included in the analyses.

<p>Overview on populations included in the analyses.</p

Population-specific MP from donors of the same population (black, donor numbers from <i>n</i> = 1,754 (Bosnia-Herzegovina) to <i>n</i> = 4,343,558 (Germany)) and increments from donors of other populations (grey) and from 500,000 additional donors of the same population (white).

<p>Populations are ordered by decreasing MP from the complete current registry, represented by the addition of black and grey columns.</p

Score plots of multivariate analysis by PCA.

<p>The t(8;21) samples are separated from the inv16 and AML-nk samples. Each patient sample was measured in triplicates and each point on the plot represents an individual measurement. The calculated sum of squares was 0.253 and 0.094 for the first and second component, respectively. The analysis was performed using SIMCA 14.0 software.</p

Description of patients.

<p>Description of patients.</p

Lipid features from extracted AML samples.

<p>(A) Saturation index of all lipids measured with shotgun MS. The analysis revealed significant changes of the mono- and polyunsaturated fatty acids in t(8;21) samples. (B) GP index of liposomes prepared from lipid extracts of various AML samples. GP is a measure of membrane order (higher GP equals more ordered membranes). t(8;21) samples exhibit lower GP values, indicating higher membrane fluidity.</p

Lipidomic approach for stratification of acute myeloid leukemia patients

<div><p>The pathogenesis and progression of many tumors, including hematologic malignancies is highly dependent on enhanced lipogenesis. De novo fatty-acid synthesis permits accelerated proliferation of tumor cells by providing membrane components but these may also alter physicochemical properties of lipid bilayers, which can impact signaling or even increase drug resistance in cancer cells. Cancer type-specific lipid profiles would permit us to monitor and interpret actual effects of lipid changes, potential fingerprints of individual tumors to be explored as diagnostic markers. We have used the shotgun MS approach to identify lipid patterns in different types of acute myeloid leukemia (AML) patients that either show no karyotype change or belong to t(8;21) or inv16 types. Differences in lipidomes of t(8;21) and inv(16) patients, as compared to AML patients without karyotype change, presented mostly as substantial modulation of ceramide/sphingolipid synthesis. Furthermore, between the t(8;21) and all other patients we observed significant changes in physicochemical membrane properties. These were related to a marked alteration in lipid saturation levels. The discovered differences in lipid profiles of various AML types improve our understanding of the pathobiochemical pathways involved and may serve in the development of diagnostic tools.</p></div

Comparison of lipid profiles of various AML types.

<p>Each point on the volcano graph represents a single lipid specie. The analysis was performed using GraphPad PRISM 6.0.</p