To detect the novel genes expressed uniquely in neutrophils and elucidate their function, the gene expression pattern was compared by using cDNA microarray containing 240 cytokine genes between the neutrophils and peripheral blood mononuclear cells (PBMCs) obtained from healthy human donors. Twenty-six genes, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were expressed in neutrophils at a level >10 times higher than that seen in phytohemagglutinin-stimulated PBMCs. The amounts of mRNA and protein of TRAIL were quantified by real-time reverse transcription-PCR and ELISA, respectively. TRAIL was expressed in resting neutrophils at the mRNA and protein levels, and its expression was enhanced after stimulation with IFN-␥. Neutrophils expressed TRAIL on the cell surface and released it into the culture media. The cytotoxicity of neutrophil-derived TRAIL against Jurkat cells was determined by flow cytometry using FITC-conjugated annexin V. When Jurkat cells were cultured with neutrophils in the presence of IFN-␥, the number of Jurkat cells undergoing apoptosis increased, and such increase depended on the effector:target ratio. This cytotoxicity was suppressed partially by adding anti-TRAIL antibody to the media. Neutrophils may exert their own antitumor effect by TRAIL. A microarray analysis was found to be a useful tool for detecting novel genes that are suggested to play unknown roles in the neutrophil function.

The prognosis of infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcomes was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group trial MLL-10 (registered at umin.ac.jp as UMIN000004801), infants with ALL were stratified into three risk groups (low-risk, LR; intermediate-risk, IR; high-risk, HR) according to KMT2A status, age, and presence of central nervous system leukemia. A modified Children's Oncology Group AALL0631 chemotherapy with addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (N=15), IR (N=19), or HR (N=56). The 3-year event-free survival (EFS) rate (standard error) for patients with KMT2A-r ALL (IR+HR) was 66.2% (5.6%) and 93.3% (6.4%) for those with KMT2A-g ALL (LR). The 3-year EFS rate was 94.4% (5.4%) for IR and 56.6% (6.8%) for HR patients. In multivariable analysis, female sex and MRD ≧0.01% at end of early consolidation were significant poor prognostic factors. Risk stratification and introduction of intensive chemotherapy in the current study were effective and able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials.

PICCs were found to provide a reliable access for prolonged intravenous administration and blood sampling in children intensively treated for hematologic and solid malignancies, thus leading to a reduction of physical pain and psychological stress in such patients. However, the long-term placement of PICCs may also be related to an increased risk of complications.

Anti-FRP mAbs induced polykaryocyte formation of U2ME-7 cells (CD4+U937 cells transfected with the HIV gpl60 gene). Anti-FRP-1 mAb immunoprecipitated gp8O-85, gpl20 and homodimers of these peptides, and anti-FRP-2 mAb reacted with gp135 identically to the A3 subunit of integrin. Both anti-FRP-1 and anti-FRP-2 mAb-induced cell fusion was blocked by anti-(l integrin antibody, fibronectin or inhibiting anti-FRP-1 antibody. Therefore, anti-FRP mAbs were thought to induce the fusion via an integrin system(s). FRP-mediated fusion was temperature, cytoskeleton, energy and Ca2+ dependent. These experiments showed a possible regulatory function of cell fusion by an integrin system(s).

The JLSG-96 study reported very low mortality rates for children newly diagnosed with multifocal Langerhans cell histiocytosis (LCH). The JLSG-02 study was performed to further improve the prognosis from 2002 to 2009. The present study compared the therapeutic results of these two studies in terms of multisystem disease. All patients were treated with 6 weeks of the Induction A regimen, comprising cytarabine, vincristine and prednisolone, followed by maintenance therapy. Poor responders to Induction A were switched to Induction B. JLSG-02 has been revised from JLSG-96 in the following respects: prednisolone dosage during Induction A increased; duration of maintenance therapy extended from 24 to 48 weeks; cyclosporine introduced to Induction B for progressive disease. One hundred forty-seven children with multisystem LCH were evaluated. Of these, 84 were positive for risk of organ involvement (RO) and 63 were RO-negative. At the 6-week point, 76.2 % of RO+ and 93.7 % of RO- patients responded to Induction A. Five-year event-free survival (EFS) was 46.2 % [95 % confidence (CI), 35.5-56.9] for RO+ and 69.7 % (58.4-81.1) for RO-, which was significantly superior to that in JLSG-96 [26.8 % (13.3-40.4) and 38.9 % (16.4-61.4), respectively]. The intensified induction and prolonged maintenance regimens in JLSG-02 improved EFS in patients with multisystem LCH.