In Vitro Generation of Haploid Germ Cells from Human XY and XXY Immature Testes in a 3D Organoid System.

Increasing survival rates of children following cancer treatment have resulted in a significant population of adult survivors with the common side effect of infertility. Additionally, the availability of genetic testing has identified Klinefelter syndrome (classic 47,XXY) as the cause of future male infertility for a significant number of prepubertal patients. This study explores new spermatogonia stem cell (SSC)-based fertility therapies to meet the needs of these patients.

propagation of XXY human Klinefelter spermatogonial stem cells: A step towards new fertility opportunities.

Klinefelter Syndrome (KS) is characterized by a masculine phenotype, supernumerary sex chromosomes (47, XXY), and impaired fertility due to loss of spermatogonial stem cells (SSCs). Early testicular cryopreservation could be an option for future fertility treatments in these patients, including SSCs transplantation or spermatogenesis. It is critically essential to adapt current SSCs propagation systems as a fertility option for KS patients.

In Vitro Propagation of XXY Undifferentiated Mouse Spermatogonia: Model for Fertility Preservation in Klinefelter Syndrome Patients.

Klinefelter syndrome (KS) is characterized by a masculine phenotype, supernumerary sex chromosomes (usually XXY), and spermatogonial stem cell (SSC) loss in their early life. Affecting 1 out of every 650 males born, KS is the most common genetic cause of male infertility, and new fertility preservation strategies are critically important for these patients. In this study, testes from 41, XXY prepubertal (3-day-old) mice were frozen-thawed.

Sudden Unexpected Death in a Child From Acute Myeloid Leukemia.

Acute myeloid leukemia can rarely cause sudden, unexpected death in children. Presentation may be non-specific and death may occur in children with no prior medical history. Herein we present the case of a previously healthy 2-year and 2 month-old White girl, who on autopsy, was found to have acute myeloid leukemia with KMT2A rearrangement extensively involving all major thoracic and abdominal organs.

Fusion Transcripts Detectable 8 Months prior to Promyelocytic Blast Crisis in Chronic Myeloid Leukemia.

Promyelocytic blast crisis arising from chronic myeloid leukemia (CML) is rare. We present a 40-year-old male who developed promyelocytic blast crisis 17 months after CML diagnosis, confirmed by the presence of the (15;17) and (9;22) translocations in the leukemic cells. Preserved nucleic acids from routine testing provided a unique opportunity to evaluate clonal progression over time.

Non-Nodal CD5-Negative Mantle Cell Lymphoma with Secondary TP53 Deletion.

Mantle cell lymphoma is a non-Hodgkin lymphoproliferative neoplasm with several clinical and morphologic variants linked, primarily, through genetic derangement of the locus. Aberrant phenotypes have been described, though prognostic data in such cohorts are limited due to a paucity of cases. We report a case of mantle cell lymphoma with non-nodal clinical presentation, aberrant loss of CD5 expression, and concomitant cytogenetic deletion of 17p.

Evaluation of Cytotoxic and Genotoxic Effects of Extremely Low-frequency Electromagnetic Field on Mesenchymal Stromal Cells.

Background: Interest in the use of extremely low-frequency (ELF) electromagnetic field (EMF) for the treatment of pain and inflammation is increasing due to the ability of this promising therapy to compete with pharmaceuticals without the adverse effects caused by drugs. However, there continues to be concerns regarding cytotoxic and genotoxic effects that may occur as a result of exposure to EMF.

Objective: To investigate this concern, we tested the effect of our known therapeutic 5 Hz, 0.

Donor-derived myeloid sarcoma in two kidney transplant recipients from a single donor.

We report the rare occurrence of donor-derived myeloid sarcoma in two kidney transplant patients who received organs from a single deceased donor. There was no evidence of preexisting hematologic malignancy in the donor at the time of organ recovery. Both recipients developed leukemic involvement that appeared to be limited to the transplanted organ.

Clinicopathological analysis of near-tetraploidy/tetraploidy acute myeloid leukaemia.

Aims: Near-tetraploidy/tetraploidy (NT/T) is a rare cytogenetic alteration in acute myeloid leukaemia (AML). NT/T-AML is categorised as complex cytogenetics and therefore, presumed to have an unfavourable prognosis. Our aim is to further characterise the clinical, morphological, cytogenetic and prognostic features of NT/T-AML.

MDM2 copy numbers in well-differentiated and dedifferentiated liposarcoma: characterizing progression to high-grade tumors.

Objectives: MDM2 gene amplification is associated with well-differentiated (WDL) and dedifferentiated liposarcomas (DDL). Using fluorescent in situ hybridization (FISH), we sought to characterize various patterns of MDM2 amplification among the morphologic spectrum of liposarcoma.

Methods: Forty-six cases of liposarcoma in various sites were examined and included 22 WDLs, 14 DLLs, and 10 negative control subjects.

Biclonal light chain gammopathy with aberrant CD33 expression in secondary plasma cell leukemia.

Plasma cell leukemia is a rare neoplastic proliferation of circulating plasma cells. Clonal proliferations of plasma cells, such as in plasma cell leukemia or plasma cell myeloma, are typically characterized by production of a monoclonal heavy and/or light chain immunoglobulin. We present a case of a secondary plasma cell leukemia arising from plasma cell myeloma with dual expression of lambda and kappa light chains along with aberrant expression of CD33, CD20, and dim CD56.

Burkitt's Lymphoma Presenting as Late-Onset Posttransplant Lymphoproliferative Disorder following Kidney and Pancreas Transplantation: Case Report and Review of the Literature.

Posttransplant lymphoproliferative disorders (PTLD) are a rare, but serious complication following transplantation. Late-onset PTLD are often associated with more monoclonal lesions and consequently have a worse prognosis. There are only isolated case reports of Burkitt's lymphoma presenting as PTLD.

New recurrent balanced translocations in acute myeloid leukemia and myelodysplastic syndromes: cancer and leukemia group B 8461.

Acquired chromosome abnormalities in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are among the most valuable determinants of diagnosis and prognosis. In search of new recurrent balanced translocations, we reviewed the Cancer and Leukemia Group B (CALGB) cytogenetics database containing pretreatment and relapse karyotypes of 4,701 adults with AML and 565 with MDS who were treated on CALGB trials. We identified all cases with balanced structural rearrangements occurring as a sole abnormality or in addition to one other abnormality, excluded abnormalities known to be recurrent, and then reviewed the literature to determine whether any of what we considered unique, previously unknown abnormalities had been reported.

inv(16)/t(16;16) acute myeloid leukemia with non-type A CBFB-MYH11 fusions associate with distinct clinical and genetic features and lack KIT mutations.

The inv(16)(p13q22)/t(16;16)(p13;q22) in acute myeloid leukemia results in multiple CBFB-MYH11 fusion transcripts, with type A being most frequent. The biologic and prognostic implications of different fusions are unclear. We analyzed CBFB-MYH11 fusion types in 208 inv(16)/t(16;16) patients with de novo disease, and compared clinical and cytogenetic features and the KIT mutation status between type A (n = 182; 87%) and non-type A (n = 26; 13%) patients.

Pdx1 and controlled culture conditions induced differentiation of human amniotic fluid-derived stem cells to insulin-producing clusters.

This study investigated the differentiation of human amniotic fluid-derived stem cells (hAFSCs) into insulin-producing clusters in vitro. Adenovirally-delivered mouse Pdx1 (Ad-Pdx1) induced human Pdx1 expression in hAFSCs and enhanced the coordinated expression of downstream β-cell markers. When Ad-Pdx1-transduced hAFSCs were sequentially treated with activin A, bFGF and nicotinamide and the culture plate surface coated with poly-l-ornithine, the expression of islet-associated human mRNAs for Pdx1, Pax6, Ngn3 and insulin was increased.

Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia.

Purpose: To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML).

Patients And Methods: We analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, and FLT3 available. We compared complete remission (CR) rates, disease-free survival (DFS), and overall survival (OS) among patients classified into the four ELN genetic groups (favorable, intermediate-I, intermediate-II, adverse) separately for 818 younger (age < 60 years) and 732 older (age ≥ 60 years) patients.

The first case described: monozygotic twin sisters with the fragile X premutation but with a different phenotype for premature ovarian failure.

Objective: To describe the first case of monozygotic twin sisters with fragile X premutation and discordance for premature ovarian failure (POF).

Design: A descriptive case study.

Setting: Academic center.

Possible role of engraftment syndrome and autologous graft-versus-host disease in myelodysplastic syndrome after autologous stem cell transplantations: retrospective analysis and review of the literature.

Background: We report a retrospective study of 452 patients with lymphoma from 1991 to 2006, with 274 men and 178 women, median age of 50 years (range, 16-76 years).

Patients And Methods: There were 85 patients with Hodgkin lymphoma (HL) and 367 with non-Hodgkin lymphoma (NHL). Eleven patients received a second autologous transplantation for progressive lymphoma, and another 4 received a second allogeneic transplantation for myelodysplastic syndrome (MDS).

The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies.

Down syndrome (DS), or trisomy 21, is a common disorder associated with several complex clinical phenotypes. Although several hypotheses have been put forward, it is unclear as to whether particular gene loci on chromosome 21 (HSA21) are sufficient to cause DS and its associated features. Here we present a high-resolution genetic map of DS phenotypes based on an analysis of 30 subjects carrying rare segmental trisomies of various regions of HSA21.

Central review of cytogenetics is necessary for cooperative group correlative and clinical studies of adult acute leukemia: the Cancer and Leukemia Group B experience.

The Cancer and Leukemia Group B has performed central review of karyotypes submitted by institutional cytogenetics laboratories from patients with acute myeloid (AML) and acute lymphoblastic (ALL) leukemia since 1986. We assessed the role of central karyotype review in maintaining accurate, high quality cytogenetic data for clinical and translational studies using two criteria: the proportion of karyotypes rejected (i.e.

Effects of mutant human Ki-ras(G12C) gene dosage on murine lung tumorigenesis and signaling to its downstream effectors.

Studies in cell culture have suggested that the level of RAS expression can influence the transformation of cells and the signaling pathways stimulated by mutant RAS expression. However, the levels of RAS expression in vivo appear to be subject to feedback regulation, limiting the total amount of RAS protein that can be expressed. We utilized a bitransgenic mouse lung tumor model that expressed the human Ki-ras(G12C) allele in a tetracycline-inducible, lung-specific manner.

Recurring translocation (10;17) and deletion (14q) in clear cell sarcoma of the kidney.

Context: Clear cell sarcoma of the kidney (CCSK) is a prognostically unfavorable renal neoplasm of childhood. Previous cytogenetic studies of CCSK have reported balanced translocations t(10;17)(q22;p13) and t(10;17)(q11;p12). Although the tumor suppressor gene p53 is located at the chromosome 17p13 breakpoint, p53 abnormalities are rarely present in these tumors.

Antimetabolite therapy for lesser-risk B-lineage acute lymphoblastic leukemia of childhood: a report from Children's Oncology Group Study P9201.

Pediatric Oncology Group (POG) protocol 9201 enrolled children with lesser-risk B-lineage acute lymphoblastic leukemia (ALL) defined by age (1-9), white blood cell count (WBC) less than 50 x 10(9)/L (50,000/microL), DNA findings of trisomies 4 and 10 (or DNA index > 1.16), and lack of overt central nervous system (CNS) leukemia. After vincristine, prednisone, and asparaginase induction, 650 of 653 eligible patients attained remission (3 induction deaths) and received 6 courses of intravenous methotrexate (1 g/m(2)) with daily mercaptopurine.

Specific extra chromosomes occur in a modal number dependent pattern in pediatric acute lymphoblastic leukemia.

Children with acute lymphoblastic leukemia (ALL) and high hyperdiploidy (>50 chromosomes) are considered to have a relatively good prognosis. The specific extra chromosomes are not random; extra copies of some chromosomes occur more frequently than those of others. We examined the extra chromosomes present in high hyperdiploid ALL to determine if there were a relation of the specific extra chromosomes and modal number (MN) and if the extra chromosomes present could differentiate high hyperdiploid from near-triploid and near-tetraploid cases.