Prospective Medicine: The Role for Genomics in Personalized Health Planning

Langheier, Jason; Snyderman, Ralph

doi:10.1517/phgs.5.1.1.25685

Cited by 25 publications

(13 citation statements)

References 30 publications

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“…1 Numerous biomarkers have been identified by genomic or proteomic approach that can subcategorize the disease phenotype and predict clinical outcome. 2 Defining a specific disease phenotype, however, does not necessarily depend on sophisticated molecular or genomic technologies.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow angiogenesis magnetic resonance imaging in patients with acute myeloid leukemia: peak enhancement ratio is an independent predictor for overall survival

Shih¹,

Hou

Liu

et al. 2009

Blood

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Emerging evidence suggests that progression of hematologic malignancies is associated with angiogenesis. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can provide global and functional imaging of tumor angiogenesis. In this study, we performed bone marrow DCE-MRI prospectively at diagnosis and after induction chemotherapy in 78 de novo acute myeloid leukemia (AML) patients and correlated it with treatment outcome. An algorithm to assess bone marrow angiogenesis by measuring the DCE-MRI time-intensity curve pixel by pixel was developed using 3 distinct parameters: peak enhancement ratio (Peak) to indicate tissue blood perfusion; amplitude (Amp) to reflect vascularity; and volume transfer constant (K trans) to indicate vascular permeability. The Peak and Amp decreased significantly at remission status after induction chemotherapy. Patients with higher Peak or Amp at diagnosis had shorter overall survival and disease-free survival than others. Cox multivariate analysis identified higher IntroductionPersonalized medicine is the final goal of translational research in the postgenomic era. 1 Numerous biomarkers have been identified by genomic or proteomic approach that can subcategorize the disease phenotype and predict clinical outcome. 2 Defining a specific disease phenotype, however, does not necessarily depend on sophisticated molecular or genomic technologies. In this study we report that by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), we are able to measure the global bone marrow angiogenesis in vivo and independently predict the clinical outcome of patients with acute myeloid leukemia (AML).It is well recognized that angiogenesis plays an important role in tumor development, progression, and metastasis. [3][4][5] Angiogenesis is one of the significant factors that correlate with the tumor aggressiveness and clinical outcome of patients with melanoma, 6 prostate cancer, 7 breast cancer, 8 and recently in leukemia or lymphomas 9,10 and multiple myeloma. [11][12][13] Microvessel density (MVD) is an assumed "gold standard" for quantification of angiogenesis in tumor tissue. MVD is increased in patients with AML with active disease in comparison to healthy controls or patients in remission. 14-17 However, MVD can be measured only in the limited area of the bone marrow biopsy specimen; thus, it cannot be used to assess the global or in vivo tumor angiogenesis. Neither the functional status of the tumor blood vessel (eg, permeability, elimination rate) could be determined by the above-mentioned immunohistochemical methods.New technologies for cancer image with functional assessment are now possible in vivo by Doppler sonography, DCE-MRI, DCE computed tomography, and fluorodeoxyglucose-18 positron emission tomography. 18-20 DCE-MRI is a noninvasive quantitative method of investigating microvascular structure and function by tracking the pharmacokinetics of injected low-molecular-weight contrast agents as they pass through the tumor vasculature. 21 This technique provides a dir...

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Section: Introductionmentioning

confidence: 99%

Bone marrow angiogenesis magnetic resonance imaging in patients with acute myeloid leukemia: peak enhancement ratio is an independent predictor for overall survival

Shih¹,

Hou

Liu

et al. 2009

Blood

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“…Analyses to track baseline risk and disease development will hopefully be incorporated into personalized health plans in the future ( Langheier and Snyderman, 2004 ). Such tracking will likely include the measurement of dynamic factors, including gene-expression, proteomics, and metabolomic assessments.…”

Section: Predictive Factorsmentioning

confidence: 99%

The Role of Genomics in Enabling Prospective Health Care

Snyderman¹

2010

Essentials of Genomic and Personalized Medicine

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“…Diese schaffen zwar die Voraussetzungen für eine prospektive Risikobeurteilung, die Identifizierung von Hochrisikopersonen, eine frühzeitige Diagnosestellung sowie eine personalisierte Gesundheitsplanung (8,18,19,23), werden bisher aber lediglich in Einzelbereichen, z. B. als Prognosemarker bei Krebserkrankungen (Philadelphia-Chromosom, BRCA1 und BRCA2), bei der Optimierung von Chemotherapien (Mercaptopurin-Dosierung bei ALL) oder dem Neugeborenenscreening durchaus erfolgreich eingesetzt.…”

Section: Prospektion Prädiktion Und Personalisierungparadigmenwandelunclassified

“…"Weg von der reaktiven, kostenintensiven und hin zur prospektiven, präventiven und individuell ausgerichteten Medizin", müsste die Devise lauten. Um dies zu verwirklichen, müssen neue Modelle einer prospektiven Gesundheitsfürsorge entworfen, getestet und validiert sowie geeignete Mechanismen der Rücker-stattung geschaffen werden (Abb.1) (8,19). …”

Section: Prospektion Prädiktion Und Personalisierungparadigmenwandelunclassified