PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation.

Unlabelled: Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival.

A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors.

Background: The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non-central nervous system tumors.

PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371.

Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. FMS-like tyrosine kinase receptor-3 (FLT3) is one of the major oncogenic receptor tyrosine kinases aberrantly activated in AML. Although protein tyrosine phosphatase PRL2 is highly expressed in some subtypes of AML compared with normal human hematopoietic stem and progenitor cells, the mechanisms by which PRL2 promotes leukemogenesis are largely unknown.

Parents' Insights into Pediatric Oncology Phase I Clinical Trials: Experiences from Their Child's Participation.

Objectives: Phase 1 clinical trials are essential in the development of novel therapies for childhood cancers. Children with cancer can participate in phase 1 clinical trials when no known curative therapy remains. Understanding the experiences of children and their families in these clinical trials can help ensure that participation supports the children's and parents' well-being.

Evidence for BCR/ABL1-positive T-cell acute lymphoblastic leukemia arising in an early lymphoid progenitor cell.

BCR-ABL1-positive leukemias have historically been classified as either chronic myelogenous leukemia or Ph+ acute lymphoblastic leukemia. Recent analyses suggest there may be a wider range of subtypes. We report a patient with BCR-ABL1 fusion positive T-cell ALL with a previously undescribed cell distribution of the fusion gene.

Imatinib mesylate for plexiform neurofibromas in patients with neurofibromatosis type 1: a phase 2 trial.

Background: Plexiform neurofibromas are slow-growing chemoradiotherapy-resistant tumours arising in patients with neurofibromatosis type 1 (NF1). Currently, there are no viable therapeutic options for patients with plexiform neurofibromas that cannot be surgically removed because of their proximity to vital body structures. We undertook an open-label phase 2 trial to test whether treatment with imatinib mesylate can decrease the volume burden of clinically significant plexiform neurofibromas in patients with NF1.

Population pharmacokinetics of intravenous ondansetron in oncology and surgical patients aged 1-48 months.

Purpose: Until recently, ondansetron was approved for the prevention of nausea and vomiting only in patients older than 2 years. However, as the use of ondansetron in patients younger than 2 years had been documented, characterization of ondansetron pharmacokinetics in this younger pediatric age group was warranted.

Methods: The pharmacokinetics of intravenously administered ondansetron were evaluated in oncology and surgical patients aged 1-48 months.

Phase I and pharmacokinetic study of gefitinib in children with refractory solid tumors: a Children's Oncology Group Study.

Purpose: Epidermal growth factor receptor is expressed in pediatric malignant solid tumors. We conducted a phase I trial of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in children with refractory solid tumors.

Patients And Methods: Gefitinib (150, 300, 400, or 500 mg/m2) was administered orally to cohorts of three to six patients once daily continuously until disease progression or significant toxicity.

Germline p53 mutation presenting as synchronous tumors.

Li-Fraumeni syndrome and the LF-like syndrome, rare heritable conditions that predispose to the development of malignancy, are associated with germline mutations of the tumor suppressor gene p53. The authors describe a 14-month-old boy who presented with synchronous rhabdomyosarcoma and adrenal cortical carcinoma and a novel mutation of the p53 gene. Analysis of exons 2 through 11 of the p53 gene using the polymerase chain reaction and DNA sequencing revealed a mutation of codon 273.

Treatment, outcome, and cost of care in children with idiopathic thrombocytopenic purpura.

Data were reviewed on treatment patterns, outcome, and hospital charges for children with idiopathic thrombocytopenic purpura (ITP). Records of 186 children with ITP, seen between January 1997 and April 2001, were reviewed. Hospital charges for initial management and first re-treatment were calculated by combining physician, hospital, and pathology charges.

Gene therapy for fanconi anemia.

Fanconi anemia is a hereditary syndrome of bone marrow failure, congenital anomalies, and a predisposition to malignancy. Most patients die from bone marrow failure. Cells from patients display a heightened sensitivity to DNA cross-linking agents with increased chromosomal breakage and increased cytotoxicity.