Dysregulated module approach identifies disrupted genes and pathways associated with acute myelocytic leukemia.

OBJECTIVE: To identify disrupted genes and pathways involved in acute myelocytic leukemia (AML) by systematically tracking the dysregulated modules across normal and AML conditions. MATERIALS AND METHODS: In this study, we firstly integrated the protein interaction data and expression profiles to infer and reweight the normal and AML networks using Pearson correlation coefficient (PCC). Next, clustering-based on maximal cliques (CMC) approach and a maximum weight bipartite matching method were implemented to infer the condition-specific modules and capture the disturbed modules, respectively, from two conditional networks. Then, the gene compositions and functional enrichment analysis were performed to identify the dysregulated genes and pathways. Finally, reverse transcription polymerase chain reaction (RT-PCR) was implemented to study the expression level of several key genes in AML patients. RESULTS: In two conditional-specific networks, universal changes of gene correlations were revealed, making the differential correlation density among disrupted module pairs. In this work, a total of 84 altered modules were identified by comparing modules in normal and AML networks. Functional enrichment analysis showed that genes in altered modules mainly involved in cell cycle, nucleic acids and cancer signaling process, and differentially expressed genes (DEGs) and changed gene correlations were mainly participated in natural killer cell-mediated cytotoxicity and acute myeloid leukemia pathway. The key genes, such as MYC, EGFR, MAPK1 and CCNA1, were all significantly differentially expressed in AML patients. CONCLUSIONS: This module approach effectively identifies dysregulated pathways and genes associated with AML. The considerable differences of gene correlations yield to these dysfunctional modules, and the coordinated disruption of these very modules contributes to leukemogenesis.

High-dose immunosuppressive therapy combined with cord blood infusion and non-myeloablative peripheral blood stem cell transplantation for patients with severe aplastic anemia.

OBJECTIVES: The aim of this study was to compare the clinical effective rates of high-dose immunosuppressive therapy combined with cord blood infusion (IS + CBI) and non-myeloablative peripheral blood stem cell transplantation (NSCT) for severe aplastic anemia (SAA). PATIENTS AND METHODS: Human leukocyte antigen (HLA)-mismatched patients received immunosuppressive therapy combined with IS + CBI, whereas those with HLA matches received NSCT. Clinical effective rates, hematopoietic recovery, and prevalence of complications were compared between the two groups. RESULTS: No significant difference in total effective rate or 2 years long-term survival was observed between the two groups. The total effective treatment in the NSCT, IS + CBI group was 80%, 68.75%, and the 2 years long-term survival rate in two groups was 2 years 76.66%, 68.75%, respectively. The median times of WBC > 1.0×109/L in the NSCT group was faster than that of IS + CBI group (13 vs 19 days) (p = 0.027). The median recovery times of PLT and Hb in the NSCT group was significantly faster than that of IS + CBI group (19 vs 50 days) (p = 0.00), (27 vs 57 days) (p = 0.001). The SAA group and the very SAA (VSAA) group did not show a significant difference in effective rate (76.74% vs 68.42%) (p = 0.490). In the NSCT group, two preparative regimens did not show a significant difference in effect (70.59% vs 92.31%) (p = 0.141). CONCLUSIONS: IS + CBI is applicable to HLA-mismatched patients with SAA. NSCT is the treatment of choice for patients with HLA matching alleles. Both treatment methods are effective on VSAA.

Experimental studies on penetrating heterokeratoplasty with human corneal grafts in monkey eyes.

In nine rhesus monkeys, human corneal grafts were used for penetrating keratoplasty in one eye of each. The data were divided into three groups according to the size of grafts. Group 1 (n = 3) received 5.5-mm human corneal grafts in 5.0-mm recipient beds; group 2 (n = 3) received 6.2-mm human corneal grafts in 6.0-mm beds; and group 3 (n = 3) received 7.5-mm grafts in 7.0-mm beds. Five of nine eyes in groups 1 and 2 (55%) maintained graft clarity for more than 1 year, but only two of the three in group 1 maintained clear human corneal grafts for 32 and 36 months, respectively. However, the three grafts in the third group maintained transparency for only 4-7 months. Our findings suggest that xenogeneic corneal grafts may have a greater success rate in humans than previously believed.