An Efficient and Robust Statistical Modeling Approach to Discover Differentially Expressed Genes Using Genomic Expression Profiles

Table 3.

Top 15 Genes Whose Expression Profiles Correlated with Differential Expression of TPO Among 11 AML Samples

Gene description Probe Z-score P-value t-test W. r.s. Relation to TPO and/or hematopoiesis
Thrombopoietin (TPO) L36051 −9.39 <0.0001 0.0971 1.000 TPO supports megakaryopoiesis, most important  regulator of platelet production (Caen et al. 1999).
Jagged 1 U73936 6.26 <0.0001 1.0000 1.0000 Jagged 1 signaling through notch 1 plays a role in  hematopoiesis (Schroeder and Just 2000).
Carboxypeptidase  (MAX.1) J04970 −5.81 <0.0001 1.0000 1.0000 MAX.1 associated with monocyte to macrophage  differentiation and is expressed in AML cells  (Rehli et al. 1995).
Dynamin 1 L07807 −5.27 0.0010 1.0000 1.0000 Dynamin 1 induced by Grb2 when monocytes  stimulated with M-CSF (Kharbanda et al. 1995).
Neutrophil gelatinase  B-associated lipocalin  (NGAL) X99133 5.24 0.0011 1.0000 1.0000 NGAL mainly expressed in myeloid cells (Bundgaard  et al. 1994), NGAL specific granules are marker for  neutrophil maturation (Le Cabec et al. 1997).
Beta 1 integrin D U33880 −5.12 0.0021 1.0000 1.0000 TPO up-regulates adhesion of hematopoetic  progenitors to fibronectin through activation of  integrin alpha4beta1 and alpha5beta1 (Gotoh  et al. 1997).
Sp4 transcription factor X68561 −5.06 0.0030 1.0000 1.0000 Sp4 not well characterized but closely related to Sp1  (Suske 1999), TPO activates several Sp1-dependent  genes during megakaryopoiesis (Wang et al. 1999).
Prothrombin M17262 4.86 0.0082 1.0000 1.0000 Thrombin cleaves TPO to various isoforms (Kato et al.  1997), thrombin and TPO may co-regulate  myeloid differentiation (van Willigen et al. 2000).
Wilms tumor 1 X69950 4.65 0.0236 1.0000 1.0000 WT1 inhibits differentiation of myeloid progenitor  cells (Tsuboi et al. 1999).
LIM-homeobox domain  (hLH-2) U11701 −4.61 0.0284 1.0000 1.0000 hLH-2 has a role in control of cell fate decision  and/or hematopoietic proliferation (Pinto do et al.  1998).
Mitochondrial creatine  kinase J04469 −4.61 0.0284 1.0000 1.0000 ?
Thrombospondin 2  (TSP2) HG896– HT896 4.61 0.0286 1.0000 1.0000 TSP2 inhibits tumor growth and angiogenesis (Streit  et al. 1999), close relative thrombospondin 1 is  negative regulator of megakaryopoiesis (Chen et  al. 1997; Touhami et al. 1997).
Lysyl hydroxylase 2  (PLOD2) U84573 4.49 0.0507 1.0000 1.0000 ?
Serotonin receptor M83181 4.33 0.1039 1.0000 1.0000 Serotonin secretion stimulated by TPO (FontenayRoupie et al. 1998).
Karyopherin beta 3 U72761 4.30 0.1192 1.0000 1.0000 ?
  • Dataset from Golub et al. (1999).

  • P-value computed from Z-score using a modified Bonferroni's correction.

  • P-value obtained from t-test with unequal variances using a modified Bonferroni's correction. When equal variances were assumed, the P-value for TPO was 0.1105 and theP-values for the other genes did not change.

  • P-value obtained from Wilcoxon rank sum using a modified Bonferroni's correction.

This Article

  1. Genome Res. 11: 1227-1236

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