Guidelines for the diagnosis and treatment of follicular lymphoma in China

Follicular lymphoma (FL) is a common subtype of B-cell lymphoma. Based on the updated National Comprehensive Cancer Network guidelines and related medical data, the authors formulated the FL guidelines for China by combining the diagnostic level and current situation of lymphoma.

Expert consensus statement on diagnosis and treatment of cancer-related depressed mood state based on Chinese medicine

This consensus statement is organized into six parts:1)Definitions:cancer-related depressed mood state is defined as a group of depressive symptoms,rather than major depressive disorder.Thus,“cancer-related depression”or“depressed mood state”is introduced as standard terminology and associated with the Chinese medicine concept of“yu zheng”(depression syndrome).2)Pathogenesis:factors including psychological stress,cancer pain,cancer fatigue,sleep disorders,surgery trauma,chemotherapy,and radiation therapy are strongly associated with cancer-related depressed mood state.Crucial elements of pathogenesis are cancer caused by depression,depression caused by cancer,and the concurrence of phlegm,dampness,and stasis from constrained liver-qi and spleen deficiency.3)Symptoms:these include core symptoms,psychological symptoms,and somatic symptoms.Depressed mood and loss of interest are the main criteria for diagnosis.4)Clinical evaluation:based on the Mini-International Neuropsychiatric Interview and a numeric rating scale,and taking mood changes during cancer diagnosis and treatment into consideration,a questionnaire can be drafted to distinguish between major depressive disorder and cancer-related depression.The aim is to assist oncology clinicians to identify,treat,and refer patients with cancer-related depression.5)Diagnosis:diagnosis should be based on the Chinese Classification for Mental Disorders(CCMD-3),taking patients’mood changes during diagnosis and treatment into consideration.6)Treatment:treatments for cancer-related depression must be performed concurrently with cancer treatment.For mild depression,non-pharmacologic comprehensive therapies,including psychological intervention,music therapy,patient education,physical activity,and acupuncture,are recommended;for moderate depression,classical Chinese herbal formulas based on syndrome pattern differentiation combined with antidepressants are suggested;for severe depressive symptoms that have progressed to major depressive disorder, patients should be referred to a psychiatric clinician for specialized care.

Identification of key genes responsible for cytokine-induced erythroid and myeloid differentiation and switching of hematopoietic stem cells by RAGE

We utilized a unique culture system to analyze the expression patterns of gene, protein, and cell surface antigen, and the biological process of the related genes in erythroid and myeloid differentiation and switching of hematopoietic stem cells （HSCs） in response to cytokine alterations. Gene-specific fragments （266） identified from five populations of cytokine-stimulated HSCs were categorized into three groups： （1） expressed specifically in a single cell population; （2） expressed in two cell populations, and （3） expressed in three or more populations. Of 145 defined cDNAs, three （2%） were novel genes. Protein two-dimensional gel electrophoresis and flow cytometry analyses showed overlapped and distinguished protein expression profiles in the cell populations studied. Biological process mapping of mRNAs expressed in erythroid and myeloid lineages indicated that mRNAs shared by both lineages attended ＇core processes,＇ whereas genes specifically expressed in either lineage alone were related to specific processes or cellular maturation. Data from this study support the hypothesis that committed HSCs （El4 or G14） cells can still be redirected to develop into myeloid or erythroid cells when erythropoietin （EPO） is replaced with granulocyte-colony stimulating factor （G-CSF） under erythroid-cultured condition or G-CSF with EPO in myeloid-cultured environment, respectively. Our results suggest that genes or proteins co-expressed in erythroid and myeloid lineages may be essential for the lineage maintenance and switching in hematopoiesis.

Zoon’s balanitis with mucinous metaplasia: A case report and review of literature

Mucinous metaplasia of the squamous epithelium of the glans penis is very rarely seen in the setting of Zoon’s balanitis. We report a case of 40 year old male with a past medical history of paroxysmal nocturnal hemoglobinuria, status-post allogeneic hematopoietic cell transplantation from an HLA-matched sibling 6 years prior to evaluation, complicated by oral and cutaneous chronic graft-versus-host disease. Mucinous metaplasia was confirmed by PAS and Mucin stains, and plasmacytosis was confirmed by immunohistochemistry for CD138 and MUM1 markers. Kappa and Lambda immunostains revealed a polyclonal pattern. The etiology of zoon’s balanitis as well as the significance of mucinous metaplasia in these setting are unclear and need to be further investigated.

Glia Maturation Factor Gamma (GMFG): A Cytokine-Responsive Protein During Hematopoietic Lineage Development and Its Func-tional Genomics Analysis

Human hematopoiesis was evaluated using the techniques of controlled stem cell differentiation, two-dimensional gel electrophoresis-based proteomics, and functional genomics. We provide the first report that glia maturation factor gamma （GMFG） is a cytokine-responsive protein in erythropoietin-induced and granulocyte-colony stimulating factor-induced hematopoietic lineage development. Results from global functional genomics analysis indicate that GMFG possesses several other features： hematopoietic tissue-specific gene expression, a promoter concentrated with high-score hematopoiesis-specific transcription factors, and possible molecular coevolution with a rudimentary blood/immune system. On the basis of our findings, we hypothesize that GMFG is a hematopoietic-specific protein that may mediate the pluripotentiality and lineage commitment of human hematopoietic stem cells.

Stem cell gene therapy:the risks of insertional mutagenesis and approaches to minimize genotoxicity

Virus-based vectors are widely used in hematopoietic stem cell(HSC)gene therapy,and have the ability to integrate permanently into genomic DNA,thus driving long-term expression of corrective genes in all hematopoietic lineages.To date,HSC gene therapy has been successfully employed in the clinic for improving clinical outcomes in small numbers of patients with X-linked severe combined immunodeficiency(SCID-X1),adenosine deaminase deficiency(ADA-SCID),adrenoleukodystrophy(ALD),thalassemia,chronic granulomatous disease(CGD),and Wiskott-Aldrich syndrome(WAS).However,adverse events were observed during some of these HSC gene therapy clinical trials,linked to insertional activation of proto-oncogenes by integrated proviral vectors leading to clonal expansion and eventual development of leukemia.Numerous studies have been performed to understand the molecular basis of vector-mediated genotoxicity,with the aim of developing safer vectors and lower-risk gene therapy protocols.This review will summarize current information on the mechanisms of insertional mutagenesis in hematopoietic stem and progenitor cells due to integrating gene transfer vectors,discuss the available assays for predicting genotoxicity and mapping vector integration sites,and introduce newlydeveloped approaches for minimizing genotoxicity as a way to further move HSC gene therapy forward into broader clinical application.