Secondary osteosarcoma arising after treatment for childhood hematologic malignancies

Secondary osteosarcoma arising after the treatment of hematologic malignancies other than Hodgkin's lymphoma is rare. We report two cases of secondary osteosarcoma arising after treatment for childhood hematologic malignancies (non-Hodgkin's lymphoma and lymphoblastic leukemia). A 10-year-old boy, at the age of 3, was diagnosed with non-Hodgkin's lymphoma. He received chemotherapy, radiation, and bone-marrow transplantation and then was in complete remission. At 6 years, he complained of increasing pain of the right thigh and was diagnosed with osteoblastic osteosarcoma. A 26-year-old man, at the age of 6, was diagnosed as having acute lymphoblastic leukemia (ALL). He received chemotherapy, radiation, and peripheral blood stem cell transplantation (PBSCT). At 11 years after PBSCT, he visited with the complaint of left lumbar swelling. He was diagnosed with chondroblastic osteosarcoma. In both cases alkaline phosphatase (ALP) had already increased prior to the onset of the symptom. We should rule out secondary osteosarcoma at the abnormal elevation of ALP during clinical follow-up of patients after treatment of childhood hematologic malignancies

Role of Misfolded N-CoR Mediated Transcriptional Deregulation of Flt3 in Acute Monocytic Leukemia (AML)-M5 Subtype

The nuclear receptor co-repressor (N-CoR) is a key component of the generic multi-protein complex involved in transcriptional control. Flt3, a key regulator of hematopoietic cell growth, is frequently deregulated in AML (acute myeloid leukemia). Here, we report that loss of N-CoR-mediated transcriptional control of Flt3 due to misfolding, contributes to malignant growth in AML of the M5 subtype (AML-M5). An analysis of hematopoietic genes in AML cells led to the identification of Flt3 as a transcriptional target of N-CoR. Flt3 level was inversely related to N-CoR status in various leukemia cells. N-CoR was associated with the Flt3 promoter in-vivo, and a reporter driven by the Flt3 promoter was effectively repressed by N-CoR. Blocking N-CoR loss with Genistein; an inhibitor of N-CoR misfolding, significantly down-regulated Flt3 levels regardless of the Flt3 receptor mutational status and promoted the differentiation of AML-M5 cells. While stimulation of the Flt3 receptor with the Flt3 ligand triggered N-CoR loss, Flt3 antibody mediated blockade of Flt3 ligand-receptor binding led to N-CoR stabilization. Genetic ablation of N-CoR potentiated Flt3 ligand induced proliferation of BA/F3 cells. These findings suggest that N-CoR-induced repression of Flt3 might be crucial for limiting the contribution of the Flt3 signaling pathway on the growth potential of leukemic cells and its deregulation due to N-CoR loss in AML-M5, could contribute to malignant growth by conferring a proliferative advantage to the leukemic blasts. Therapeutic restoration of N-CoR function could thus be a useful approach in restricting the contribution of the Flt3 signaling pathway in AML-M5 pathogenesis

their mother's maternal aunt with a female phenotype

Objective: To present a familial case of Swyer syndrome.Design: Case report.Setting: Academic medical center.Patient(s): Two sisters with a main complaint of primary amenorrhea and another case, their mother's maternal aunt with the same history of primary amenorrhea but married with no consanguinity and no children.Intervention(s): None.Main Outcome Measure(s): The patients were studied from clinical, endocrinologic, and genetic perspectives.Result(s): Chromosome analyses revealed a 46, XY male karyotype with no detectable mosaicism in both sisters and their mother's maternal aunt. Molecular studies of sex-determining region Y and molecular investigation undertaken for the two sisters revealed SRY negativity.Conclusion(s): Gonadal dysgenesis can also be inherited as an X-linked disorder, and evidence exists from familial studies of perhaps autosomal inheritance. (Fertil Steril (R) 2011; 95: 1786. e1-e3. (C) 2011 by American Society for Reproductive Medicine.

Complete gonadal dysgenesis 46,xy in two sisters and their mothers' maternal aunt with a female phenotype

Abstract Not Availabl

Aplasia Ras Homologous Member I Gene and Development of Glial Tumors

The ARHI (aplasia Ras homologue member I, also known as DIRAS3) gene shows 60.0% sequence homology to the Ras proto-oncogene and was the first mater-nally-imprinted tumor suppressor gene identified in the Ras family. It is constitutively expressed from the paternal allele in normal breast, ovary, heart, liver, pancreas, thyroid and brain tissues, and is lost or markedly down-regulated primarily in breast, ovarian, pancreas and thyroid tumor tissues. We have investigated the expression, LOH (loss of heterozygosity) and methylation status of this gene in glial tumors and peripheral blood samples of 21 patients, and in seven normal brain tissue samples. Gene expression by real time reverse transcriptase polymerase chain reaction (RT-PCR) was found to be increased in 14 and decreased in seven of the 21 tumors. The LOH was detected by fragment analysis, using five labeled polymorphic markers specific for the 1p31 region, in two of the tumors. Methylation status of the CpG island I, II and III was evaluated using COBRA (combined bisulfite restriction analysis) and RFLP (restriction fragment length polymorphism) in 21 tumors and also a hypermethylated healthy volunteer as a positive control, revealed that only two tumors had hypermethylation in CpG island I (of which one also had LOH). These results suggest that LOH and hypermethylation may be one mechanism of silencing the ARHI gene expression and development of glial tumor development.PubMedWoSScopu