Severe acute respiratory syndrome (SARS) is a public health concern worldwide. By studying the human leukocyte antigen (HLA) types A, B, DR, and DQ alleles in 90 Chinese patients with serologically confirmed SARS infections, we identified a strong association between HLA-B*0703 (OR, 4.08; 95% CI, 2.03-8.18;[Bonferroni-corrected P p .00072 P value, P c ! .0022]) and -DRB1*0301 (OR, 0.06; 95%, 0.01-0.47;[after Bonferroni correction, ]) P p .00008 P ! .0042 and the development of SARS. Moreover, the frequency of B*0703 and B60 coinheritance (9.6%; 95% CI, 4.6%-19.0%) in our SARS group was significantly higher ( ) Ϫ9 P p 3 ϫ 10 than that expected in the general population (0.4%). These genetic data will critically affect both the study of the pathogenesis of SARS and the design of vaccination programs.

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RUNX3/AML2 is a Runt domain transcription factor like RUNX1/AML1 and RUNX2/ AML3. Regulated by 2 promoters P1 and P2, RUNX3 is frequently inactivated by P2 methylation in solid tumors. Growing evidence has suggested a role of this transcription factor in hematopoiesis. However, genetic alterations have not been reported in blood cancers. In this study on 73 acute myeloid leukemia (AML) patients (44 children and 29 adults), we first showed that high RUNX3 expression among childhood AML was associated with a shortened event-free survival, and RUNX3 was significantly underexpressed in the prognostically favorable subgroup of AML with the t(8;21) and inv(16) translocations. We further demonstrated that this RUNX3 repression was mediated not by P2 methylation, but RUNX1-ETO and CBF␤-MYH11, the fusion products of t(8; 21) and inv(16), via a novel transcriptional mechanism that acts directly or indirectly in collaboration with RUNX1, on 2 conserved RUNX binding sites in the P1 promoter. In in vitro studies, ectopically expressed RUNX1-ETO and CBF␤-MYH11 also inhibited endogenous RUNX3 expression. Taken together, RUNX3 was the first transcriptional target found to be commonly repressed by the t(8;21) and inv (16) IntroductionThe Runt domain transcription factor family includes RUNX1/ AML1, RUNX2/AML3, and RUNX3/AML2. These transcription factors share a conserved Runt domain for binding to a 6-base pair (bp) DNA sequence (TGT/cGGT) and heterodimerization with core-binding factor ␤ (CBF␤). CBF␤ does not bind DNA directly but increases the ability of RUNX proteins to bind DNA and regulate transcription. 1 RUNX1 and RUNX2 are essential for hematopoiesis and osteogenesis, respectively. 2,3 Moreover, RUNX1 regulates neuron and muscle function. 4,5 On the other hand, RUNX3 is involved in neurogenesis and thymopoiesis and acts as a tumor suppressor in gastric cancer. [6][7][8] In addition, RUNX3 is inactivated frequently by promoter methylation and less frequently by gene deletion, point mutations, and protein mislocalization in various solid tumors. 9 RUNX3 and RUNX1 show prominent expression in hematopoietic cells and different subsets of neurons, 4,10 while RUNX2 is expressed mainly in bone and also other tissues including hematopoietic stem cells. 11 The expression of RUNX3 and RUNX1 can be induced by retinoic acid, suggesting that these transcription factors may jointly regulate retinoic acid-mediated hematopoietic differentiation. 10 The functional overlap was supported by the observations that hematopoietic defects due to RUNX1 deficiency could be rescued by RUNX3. 12,13 Further evidence suggesting a role of RUNX3 in hematopoiesis was reduction of mature blood cell formation in zebrafish by RUNX3 depletion. 14 The role of RUNX3 in tumorigenesis and its potential involvement in hematopoiesis suggest a role of this transcription factor in hematological malignancies. However, genetic alterations of RUNX3 have not been reported in acute myeloid leukemia (AML). 15 t(8;21)(q22;q22) and inv(16)(p13;q22) are the 2 most common t...