The Clinical Utility of Mutation Testing in Acute Leukemia: A Canadian Consensus.

FMS-like tyrosine kinase 3 () mutations are detected in approximately 20-30% of patients with acute myeloid leukemia (AML), with the presence of a internal tandem duplication (-ITD) mutation being associated with an inferior outcome. Assessment of mutational status is now essential to define optimal upfront treatment in both newly diagnosed and relapsed AML, to support post-induction allogeneic hematopoietic stem cell transplantation (alloSCT) decision-making, and to evaluate treatment response via measurable (minimal) residual disease (MRD) evaluation. In view of its importance in AML diagnosis and management, the Canadian Leukemia Study Group/Groupe canadien d'étude sur la leucémie (CLSG/GCEL) undertook the development of a consensus statement on the clinical utility of mutation testing, as members reported considerable inter-center variability across Canada with respect to testing availability and timing of use, methodology, and interpretation.

Systematic Scoping Review of Studies Reporting Unexpected Donor-Derived Abnormalities from Recipients of Allogeneic Hematopoietic Cell Transplantation: A Proposed Framework for Donor Disclosure.

Allogeneic hematopoietic cell transplantation (HCT) is used increasingly to treat blood and immune-based disorders. Post-transplantation testing of HCT recipients can lead to unexpected molecular, cytogenetic, and other information in donor-derived cells, raising questions regarding the potential impact on donor health. This study was conducted to identify the breadth of donor-derived abnormalities identified by testing HCT recipients and to determine the extent to which disclosure and donor follow-up are described.

An Unusual Case of Obstructive Shock.

A 54-year-old man presented in profound obstructive shock. Investigations revealed a right atrial mass causing severe right ventricular inflow obstruction and compromised cardiac output. The patient was treated with emergency balloon catheter intervention to relieve the obstruction, with resulting hemodynamic stability.

Anaplastic large cell lymphoma as a posttransplant lymphoproliferative disorder in a renal transplant patient: A case report.

We report a case of a 45-year-old female who developed an ALK-positive anaplastic large cell lymphoma (ALCL) 9 years after renal transplant. The patient underwent a cadaveric renal transplant for diabetic nephropathy, and presented 9 years later with fever and multiorgan dysfunction. The initial CT scans showed multiple enlarged supra- and infradiaphrgamatic lymph nodes.

Utilising red cell antigen genotyping and serological phenotyping in sickle cell disease patients to risk-stratify patients for alloimmunisation risk.

Background: Alloimmunisation and haemolytic transfusion reactions (HTRs) can occur in patients with sickle cell disease (SCD) despite providing phenotype-matched red blood cell (RBC) transfusions. Variant RBC antigen gene alleles/polymorphisms can lead to discrepancies in serological phenotyping. We evaluated differences between RBC antigen genotyping and phenotyping methods and retrospectively assessed if partial antigen expression may lead to increased risk of alloimmunisation and HTRs in SCD patients at a tertiary centre in Canada.

Implementation of an NGS-based sequencing and gene fusion panel for clinical screening of patients with suspected hematologic malignancies.

Objectives: The diagnosis of hematologic malignancies integrates multiple diagnostic and clinical disciplines. Historically, targeted (single-analyte) genetic testing has been used as reflex to initial prescreening by other diagnostic modalities including flow cytometry, anatomic pathology, and clinical cytogenetics. Given the wide range of mutations associated with hematologic malignancies a DNA/RNA-based NGS panel can provide a more effective and economical approach to comprehensive testing of patients as an initial, tier-1 screen.

Laboratory assessment of multiple myeloma.

Laboratory testing plays an essential role in the diagnosis and management of patients with multiple myeloma. A variety of chemistry and molecular assays are routinely used to monitor patient progress, response to treatment and relapse. Here, we have reviewed current literature and core guidelines on the details of laboratory testing in myeloma-related investigations.

Resolving variable maternal D typing using serology and genotyping in selected prenatal patients.

Background: RhIG prophylaxis for D- pregnant women prevents hemolytic disease of the newborn and typically depends on results of serologic D typing. Interpretation and follow-up of weak D serology is variable. Recent recommendations promote genotyping for RHD status determination in those with weak D serology.

Weak D type 67 in four related Canadian blood donors.

Correct donor D typing is critical to prevent recipient alloimmunization. No method can detect all variants, and the immunogenicity of many variants is unknown. Routine ABO and D serologic typings are performed in our laboratory by automated microplate testing.

Acute extravascular hemolytic transfusion reaction due to anti-Kpa antibody missed by electronic crossmatch.

Background: Kpa antigen is a low incidence red blood cell antigen within the Kell system. Anti-Kpa alloantibody may be associated with acute and delayed hemolytic transfusion reactions.

Case Study: We report a case of a clinically significant acute extravascular hemolytic transfusion reaction mediated by previously unrecognized (and undetected) anti-Kpa alloantibody.

Dissemination of intraperitoneal ovarian cancer: Discussion of mechanisms and demonstration of lymphatic spreading in ovarian cancer model.

Ovarian cancer is often accompanied by severe ascites. This complication aggravates the disease per se and the chances for its successful treatment. The etiology of ascites is not well understood nor are efficient therapies for ascites available.

ING1a expression increases during replicative senescence and induces a senescent phenotype.

The ING family of tumor suppressor proteins affects cell growth, apoptosis and response to DNA damage by modulating chromatin structure through association with different HAT and HDAC complexes. The major splicing isoforms of the ING1 locus are ING1a and INGlb. While INGlb plays a role in inducing apoptosis, the function of ING1a is currently unknown.

Chromatin modification and senescence: linkage by tumor suppressors?

Senescence was originally defined as a state associated with cell cycle arrest that occurs after cells have undergone an intrinsically limited number of divisions in vitro. Much evidence indicates that senescence occurs as a consequence of the internal stress signal generated from shortening telomeres on the ends of chromosomes. However, more recently, various forms of extrinsic stresses have been shown to induce a markedly similar senescent phenotype that includes changes in chromatin structure and gene expression.

Grow-ING, Age-ING and Die-ING: ING proteins link cancer, senescence and apoptosis.

The INhibitor of Growth (ING) family of plant homeodomain (PHD) proteins induce apoptosis and regulate gene expression through stress-inducible binding of phospholipids with subsequent nuclear and nucleolar localization. Relocalization occurs concomitantly with interaction with a subset of nuclear proteins, including PCNA, p53 and several regulators of acetylation such as the p300/CBP and PCAF histone acetyltransferases (HATs), as well as the histone deacetylases HDAC1 and hSir2. These interactions alter the localized state of chromatin compaction, subsequently affecting the expression of subsets of genes, including those associated with the stress response (Hsp70), apoptosis (Bax, MDM2) and cell cycle regulation (p21WAF1, cyclin B) in a cell- and tissue-specific manner.

BARD1 induces apoptosis by catalysing phosphorylation of p53 by DNA-damage response kinase.

The BRCA1-associated RING domain protein BARD1 acts with BRCA1 in double-strand break repair and ubiquitination. BARD1 plays a role as mediator of apoptosis by binding to and stabilizing p53, and BARD1-repressed cells are resistant to apoptosis. We therefore investigated the mechanism by which BARD1 induces p53 stability and apoptosis.

A novel transcriptional inhibitory element differentially regulates the cyclin D1 gene in senescent cells.

Senescent human diploid fibroblasts are unable to initiate DNA synthesis following mitogenic stimulation and adopt a unique gene expression profile distinct from young or quiescent cells. In this study, a novel transcriptional regulatory element was identified in the 5'-untranslated region of the cyclin D1 gene. We show that this element differentially suppresses cyclin D1 expression in young versus senescent fibroblasts.