Myelodysplastic/myeloproliferative neoplasms

Overview of myelodysplastic/myeloproliferative neoplasms detailing clinical, pathologic, cytogenetic, and molecular findings

Functional and genetic screening of acute myeloid leukemia associated with mediastinal germ cell tumor identifies MEK inhibitor as an active clinical agent

Table of genes tested by the next-generation sequencing panel. (PPTX 58.1 kb

Case Report: ASXL1, RUNX1, and IDH1 mutation in tyrosine kinase-independent resistant chronic myeloid leukemia progressing to chronic myelomonocytic leukemia-like accelerated phase

Although the majority of patients with chronic myeloid leukemia (CML) enjoy an excellent prognosis tyrosine kinase inhibitor (TKI) therapy, resistance remains a significant clinical problem. Resistance can arise from mutations in the kinase domain of ABL preventing drug binding, or due to ill-defined kinase-independent mechanisms. In this case report, we describe the case of a 27-year-old woman with a long-standing history of chronic phase (CP) CML who developed kinase-independent resistance with mutations in ASXL1 and RUNX1. As a consequence of uncontrolled disease, she progressed to a chronic myelomonocytic leukemia-like (CMML) accelerated phase (AP) disease with the acquisition of a mutation in IDH1. This disease progression was associated with the development of an inflammatory serositis, a phenomenon that has been described in CMML but not in AP-CML. This case presents key features of kinase-independent resistance with insight into potential mechanisms, highlights management challenges, and describes a novel systemic inflammatory response that occurred in this patient upon disease progression

The Role of Molecular Pathology in the Diagnosis of Cutaneous Lymphomas

Primary cutaneous lymphomas can be difficult to be distinguished from reactive mimics, even when integrating histologic, immunophenotypic, and clinical findings. Molecular studies, especially PCR-based antigen receptor gene rearrangement (ARGR) analysis, are frequently useful ancillary studies in the evaluation of cutaneous lymphoproliferations. The biologic basis of ARGR studies is discussed, as well as a comparison of various current protocols. The pitfalls and limitations of ARGR analysis are also highlighted. Recent advances in the understanding of the molecular pathogenesis of various cutaneous lymphomas are discussed. Some of these nascent discoveries may lead to the development of diagnostically useful molecular assays

Overexpression of Pre-Pro-Cholecystokinin Stimulates β-Cell Proliferation in Mouse and Human Islets with Retention of Islet Function

Type 1 and type 2 diabetes result from a deficit in insulin production and β-cell mass. Methods to expand β-cell mass are under intensive investigation for the treatment of type 1 and type 2 diabetes. We tested the hypothesis that cholecystokinin (CCK) can promote β-cell proliferation. We treated isolated mouse and human islets with an adenovirus containing the CCK cDNA (AdCMV-CCK). We measured [3H]thymidine and BrdU incorporation into DNA and additionally, performed flow cytometry analysis to determine whether CCK overexpression stimulates β-cell proliferation. We studied islet function by measuring glucose-stimulated insulin secretion and investigated the cell cycle regulation of proliferating β-cells by quantitative RT-PCR and Western blot analysis. Overexpression of CCK stimulated [3H]thymidine incorporation into DNA 5.0-fold and 15.8-fold in mouse and human islets, respectively. AdCMV-CCK treatment also stimulated BrdU incorporation into DNA 10-fold and 21-fold in mouse and human β-cells, respectively. Glucose-stimulated insulin secretion was unaffected by CCK expression. Analysis of cyclin and cdk mRNA and protein abundance revealed that CCK overexpression increased cyclin A, cyclin B, cyclin E, cdk1, and cdk2 with no change in cyclin D1, cyclin D2, cyclin D3, cdk4, or cdk6 in mouse and human islets. Additionally, AdCMV-CCK treatment of CCK receptor knockout and wild-type mice resulted in equal [3H]thymidine incorporation. CCK is a β-cell proliferative factor that is effective in both mouse and human islets. CCK triggers β-cell proliferation without disrupting islet function, up-regulates a distinct set of cell cycle regulators in islets, and signals independently of the CCK receptors