Julianne Qualtieri

High Prevalence of Obesity in Acute Promyelocytic Leukemia (APL): Implications for Differentiating Agents in APL and Metabolic Syndrome

Background: Between January 1999 and December 2008, 469 patients treated for acute myeloid leukemia (AML) were included in this single-institution study. Methods: We performed a case–control analysis to study the rate of obesity among patients with acute promyelocytic leukemia (APL) and non-APL AML. Results: A total of 81% of APL patients analyzed were obese compared with 41.7% in the non-APL group (p < 0.001). Body mass index (BMI) >30 was seen in 57% of APL patients compared with 31% for the non-APL group (p = 0.01). Neither obesity nor the chemotherapy dosing based on ideal body weight affected survival. Conclusions: Our findings generate the hypothesis that APL and metabolic syndromes may share a common pathogenic pathway via retinoic acid receptors (RARs), the ligand-controlled transcription factors that function as heterodimers with retinoid X receptors (RXRs) to regulate cell growth and survival. If this link is confirmed in larger studies, our data will instigate further studies using RXR and RAR modulators as a preventive strategy among obese individuals.

A Case of Multiple Myeloma with Metachronous Chronic Myeloid Leukemia Treated Successfully with Bortezomib, Dexamethasone, and Dasatinib

The coexistence of multiple myeloma and chronic myeloid leukemia in a single patient is a very rare event that has been reported very infrequently in the literature. We report a case of a patient who developed chronic myeloid leukemia four years after his diagnosis with multiple myeloma. Historically, no link between the two malignancies has been identified. This synchronous existence complicates the treatment plan for these patients, and there is a lack of evidence on the best therapeutic approach. Our patient was successfully treated with a combination of bortezomib, dexamethasone, and dasatinib, which he tolerated well for eleven months until he eventually succumbed to cardiac complications and pulmonary hypertension leading to his death.

Decreased plasma DEK Oncogene Levels Correlate with p16-Negative Disease and Advanced Tumor Stage in a Case–Control Study of Patients with Head and Neck Squamous Cell Carcinoma

Head and neck cancer (HNC) remains the sixth most common malignancy worldwide and survival upon recurrence and/or metastasis remains poor. HNSCC has traditionally been associated with alcohol and nicotine use, but more recently the Human Papilloma Virus (HPV) has emerged as a favorable prognostic risk factor for oropharyngeal HNSCC. However, further stratification with additional biomarkers to predict patient outcome continues to be essential. One candidate biomarker is the DEK oncogenic protein, which was previously detected in the urine of patients with bladder cancer and is known to be secreted by immune cells such as macrophages. Here, we investigated if DEK could be detected in human plasma and if DEK levels correlated with clinical and pathological variables of HNSCC. Plasma was separated from the peripheral blood of newly diagnosed, untreated HNSCC patients or age-matched normal healthy controls and analyzed for DEK protein using ELISA. Plasma concentrations of DEK protein were lower in p16-negative tumors compared to both normal controls and patients with p16-positive tumors. Patients with lower plasma concentrations of DEK were also more likely to have late stage tumors and a lower white blood cell count. Contrary to previously published work demonstrating a poor prognosis with high intratumoral DEK levels, we show for the first time that decreased concentrations of DEK in patient plasma correlates with poor prognostic factors, including HPV-negative status as determined by negative p16 expression and advanced tumor stage.

A defect in KCa3.1 channel activity limits the ability of CD8+ T cells from cancer patients to infiltrate an adenosine-rich microenvironment

Adenosine strongly inhibits the migration of T cells from cancer patients due to reduced KCa3.1 K+ channel activity. Reduced K+ channel activity curbs T cell migration T cell accumulation in solid tumors is limited by multiple factors found within the tumor microenvironment, including the nucleoside adenosine. Chimote et al. analyzed the migration of CD8+ T cells in a 3D chemotaxis assay and found that adenosine inhibited the chemotaxis of T cells from cancer patients more than T cells from healthy donors. The increased sensitivity of patient CD8+ T cells to adenosine correlated with reduced KCa3.1 potassium (K+) channel activity, but not adenosine receptor expression or signaling. Treatment with a KCa3.1 channel agonist restored patient CD8+ T cell migration in the presence of adenosine, suggesting that K+ channel activators may help augment T cell infiltration of adenosine-rich solid tumors. The limited ability of cytotoxic T cells to infiltrate solid tumors hampers immune surveillance and the efficacy of immunotherapies in cancer. Adenosine accumulates in solid tumors and inhibits tumor-specific T cells. Adenosine inhibits T cell motility through the A2A receptor (A2AR) and suppression of KCa3.1 channels. We conducted three-dimensional chemotaxis experiments to elucidate the effect of adenosine on the migration of peripheral blood CD8+ T cells from head and neck squamous cell carcinoma (HNSCC) patients. The chemotaxis of HNSCC CD8+ T cells was reduced in the presence of adenosine, and the effect was greater on HNSCC CD8+ T cells than on healthy donor (HD) CD8+ T cells. This response correlated with the inability of CD8+ T cells to infiltrate tumors. The effect of adenosine was mimicked by an A2AR agonist and prevented by an A2AR antagonist. We found no differences in A2AR expression, 3′,5′-cyclic adenosine monophosphate abundance, or protein kinase A type 1 activity between HNSCC and HD CD8+ T cells. We instead detected a decrease in KCa3.1 channel activity, but not expression, in HNSCC CD8+ T cells. Activation of KCa3.1 channels by 1-EBIO restored the ability of HNSCC CD8+ T cells to chemotax in the presence of adenosine. Our data highlight the mechanism underlying the increased sensitivity of HNSCC CD8+ T cells to adenosine and the potential therapeutic benefit of KCa3.1 channel activators, which could increase infiltration of these T cells into tumors.

Differential expression of ribosomal proteins in myelodysplastic syndromes

Aberrations of ribosomal biogenesis have been implicated in several congenital bone marrow failure syndromes, such as Diamond–Blackfan anaemia, Shwachman–Diamond syndrome and Dyskeratosis Congenita. Recent studies have identified haploinsufficiency of RPS14 in the acquired bone marrow disease isolated 5q minus syndrome, a subtype of myelodysplastic syndromes (MDS). However, the expression of various proteins comprising the ribosomal subunits and other proteins enzymatically involved in the synthesis of the ribosome has not been explored in non-5q minus MDS. Furthermore, differences in the effects of these expression alterations among myeloid, erythroid and megakaryocyte lineages have not been well elucidated. We examined the expression of several proteins related to ribosomal biogenesis in bone marrow biopsy specimens from patients with MDS (5q minus patients excluded) and controls with no known myeloid disease. Specifically, we found that there is overexpression of RPS24, DKC1 and SBDS in MDS. This overexpression is in contrast to the haploinsufficiency identified in the congenital bone marrow failure syndromes and in acquired 5q minus MDS. Potential mechanisms for these differences and aetiology for these findings in MDS are discussed.

Left atrial thrombus mimicking atrial myxoma on imaging studies in a patient with cardiac transplant

Left atrial thrombus can develop in patients with atrial fibrillation and/or a dilated left atrium such as seen in patients with heart failure. In cardiac transplant patients with bi-atrial anastomosis, the suture line can be a potential nidus for thrombus formation. These thrombi can be either organized or unstable with ulcerated surfaces. We present a unique case of a left atrial mass in a cardiac transplant patient with features of atrial myxoma on imaging studies but found to be an organized thrombus on histopathology. <Learning objective: Left atrial thrombus formation in the cardiac transplant patient is a rare but serious condition. Most of the times it can be diagnosed with imaging studies but these noninvasive studies do not always give a definite diagnosis. We present a unique case of left atrial thrombus presenting as classic imaging features of atrial myxoma diagnosed after surgical resection. We emphasize that while treating these patients broad differential diagnosis should always be considered.>.

Lymphoma Presenting as Secondary HLH: A Review With a Tale of Two Cases

Lymphoma-associated hemophagocytic syndrome is a disease with an extremely poor prognosis and can be easily missed at diagnosis. Identifying and treating the underlying lymphoma early is of utmost importance because that directly affects outcome. Thorough and repeated testing for the underlying cause is imperative. Further studies are necessary to better understand the most appropriate front-line therapy. Allogeneic bone marrow transplant has shown promising results in children and needs to be studied further in adults.