Nucleophosmin (NPM) mutations have been found in a significant proportion of adults with de novo acute myeloid leukemia (AML), especially in those of a normal karyotype. These results provide a basis for studies of the pathogenesis in this specific subgroup of AML. In this study, NPM mutations were analyzed in 173 Chinese patients of de novo AML, including adults and children. We found that NPM mutations were present in 19.1% of the overall population and 40.3% of those with a normal karyotype. Adults had a significantly higher incidence of NPM mutations than children [32 of 126 (25.4%) versus 1 of 47 (2.1%), P < 0.001]. NPM mutations were closely associated with normal karyotype (P < 0.001) and internal tandem duplication of FLT3 (P = 0.002), but negatively associated with CEBPA mutations (P = 0.032) and expression of CD34 (P < 0.001) and HLA-DR (P = 0.003). Serial analyses of NPM mutations showed the mutation disappeared at complete remission, but the same mutation reappeared at relapse, except for one who lost the mutation at the second relapse, when new cytogenetic abnormalities emerged. None acquired novel mutations during the follow-up period. In conclusion, NPM mutations occur in an age-dependent fashion. Moreover, the findings that NPM mutations are stable during disease evolution and closely associated with disease status make it a potential marker for monitoring minimal residual disease. (Cancer Res 2006; 66(6): 3310-6)

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Independent pharmacogenomic determinants associated with treatment outcome were identified in subsets of Taiwanese ALL patients.

Thick film thermistors based on the thermistor powder of the sintered ceramic thermistor, prepared from oxides of nickel, cobalt and manganese, were fabricated and studied. The ingredient compositions, including the composition proportions, influenced the properties of thick film thermistors. The effects of the compositions of the sintered ceramic thermistors, the amounts of additives used and the compositions of the glass binders on the properties of the thick film thermistors were also studied.

Inappropriate expression of microRNAs (miRNAs) is strongly associated with leukemogenesis. miRNAs (miRs)-143 and -145, previously shown to be reduced in colon cancers, have been demonstrated recently to be down-regulated in B-cell malignancies including chronic lymphoblastic leukemia, B-cell lymphoma, Burkitt’s lymphoma. In this study, we determined the role of miR-143 and miR-145 in childhood leukemia treated by the standard TPOG (Taiwan Pediatric Oncology Group)-2002 protocols approved for treatment of patients in Taiwan. Ten patients with childhood B-lineage ALL and four ALL leukemia cells lines including REH (CRL-8286TM), CCRF-SB (CCL-120TM), RS4 (CRL-1873TM), and SUP-B15 (CRL-1929) were measured for the miRNA expression using a TagMan quantitative RT-PCR method. Our results showed that miR-143 and miR-145 were both down-regulated 0.09 and 0.19 times individually (n= 13, p &lt;0.001 and p = 0.011) in mononuclear cells in bone marrow of newly-diagnosed and relapsed samples in comparison with the same cell types of remission samples (n=16). To examine possible suppressive functions of miR-143 and miR-145 with respect to cell growth, the REH cells were used for expression with precursor form and mature form miR-143 and miR-145, and subsequently measured for cell growth rate. Preliminary results showed that the two miRNAs did not alter the growth rate of the REH over-expressing either miRNA. Taken together, we have identified miR-143 and miR-145 as biomarkers that may differentiate malignant and normal B cells. miR-143 and miR-145 may contribute to leukemogenesis in childhood B-lineage ALL by new yet to be defined mechanisms.