HLH and TET2 Mutation Presenting after First Cycle of CLL Treatment.

Here we report development of hemophagocytic lymphohistiocytosis (HLH), along with unmasking of a TET2-mutated myeloid neoplasm, after initial doses of bendamustine and rituximab for longstanding chronic lymphocytic leukemia (CLL). After many years of CLL showing minimally progressive lymphocytosis, the patient's white blood cell count began to decline in parallel with neutrophil count, hemoglobin, and platelet count. Bone marrow biopsy showed partial CLL involvement; bendamustine+rituximab therapy was augmented with granulocyte colony-stimulating factor (g-CSF) and romiplostim to mitigate worsening pancytopenia, without response.

Gelatinous bone marrow transformation secondary to unusual eating habits and drastic weight loss.

Gelatinous bone marrow transformation (GMT), also known as starvation bone marrow, has been reported in a number of chronic illnesses, eating disorders (anorexia nervosa) and malignancies. We report the case of a 37-year-old man with a history of bipolar disorder and obesity (weighing >300 pounds) who presented due to recently developing a deep yellow colour to his skin. Over the past 2 years, through diet and exercise, he lost over 150 pounds.

HOX proteins and leukemia.

HOX and three amino acid loop extension (TALE) proteins cooperate to induce transformation in mouse leukemia models, and are dysregulated in a variety of human leukemias. Despite decades of research, the mechanism of action for Hox proteins in embryogenesis and hematopoiesis remains unclear. Recent studies on the roles of Hoxa9 and Meis1 in leukemia has led to a wealth of new data, but their molecular mechanisms of action and synergy remain obscure.

Structural basis of multimer-mediated mayhem.

Oligomerization of AML1-ETO contributes to leukemogenesis through obscure mechanisms. In this issue of Cancer Cell, Bushweller and colleagues show the crystal structure of the ETO NHR2 domain to be a tetramer. Tetramer formation is important for maturation arrest and self-renewal, and gene expression is altered in the absence of self-association.

p300/CBP-associated factor drives DEK into interchromatin granule clusters.

DEK is a mammalian protein that has been implicated in the pathogenesis of autoimmune diseases and cancer, including acute myeloid leukemia, melanoma, glioblastoma, hepatocellular carcinoma, and bladder cancer. In addition, DEK appears to participate in multiple cellular processes, including transcriptional repression, mRNA processing, and chromatin remodeling. Sub-nuclear distribution of this protein, with the attendant functional ramifications, has remained a controversial topic.

Minireview: DEK and gene regulation, oncogenesis and AIDS.

A brief review summarizing the relationships that exist between the DEK protein and gene regulation, oncogenesis and AIDS.

YY1 and NF-Y binding sites regulate the transcriptional activity of the dek and dek-can promoter.

The mammalian protein DEK has been implicated in multiple cellular processes, including transcriptional regulation, mRNA processing, and chromatin remodeling, and is associated with a number of clinical autoimmune and neoplastic conditions. The connection between DEK and cancer exists at multiple levels: (a) the t(6;9) chromosomal translocation that characterizes a subtype of acute myelogenous leukemia cases results in the formation of a DEK-CAN fusion oncoprotein; (b) a fragment of dek cDNA is capable of partially reversing the radiation-sensitive phenotype of fibroblasts cultured from ataxia-telangiectasia patients; and (c) increased levels of dek mRNA have been found to be associated with hepatocellular carcinoma, glioblastoma, and melanoma. Despite the growing list of cancer subtypes with a connection to DEK, the factors that mediate its expression have yet to be characterized.